| 1. |
- Acs, Balazs, et al.
(author)
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Variability in Breast Cancer Biomarker Assessment and the Effect on Oncological Treatment Decisions: A Nationwide 5-Year Population-Based Study
- 2021
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In: Cancers. - : MDPI AG. - 2072-6694. ; 13:5
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Journal article (peer-reviewed)abstract
- We compared estrogen receptor (ER), progesterone receptor (PR), human epidermal growth-factor receptor 2 (HER2), Ki67, and grade scores among the pathology departments in Sweden. We investigated how ER and HER2 positivity rates affect the distribution of endocrine and HER2-targeted treatments among oncology departments. All breast cancer patients diagnosed between 2013 and 2018 in Sweden were identified in the National Quality Register for Breast Cancer. Cases with data on ER, PR, HER2, Ki67, grade, and treatment were selected (43,261 cases from 29 departments following the guidelines for biomarker testing). The ER positivity rates ranged from 84.2% to 97.6% with 6/29 labs out of the overall confidence intervals (CIs), while PR rates varied between 64.8% and 86.6% with 7/29 labs out of the CIs. HER2 positivity rates ranged from 9.4% to 16.3%, with 3/29 labs out of the overall CIs. Median Ki67 varied between 15% and 30%, where 19/29 labs showed significant intra-laboratory variability. The proportion of grade-II cases varied between 42.9% and 57.1%, and 13/29 labs were outside of the CI. Adjusting for patient characteristics, the proportion of endocrine and anti-HER2 treatments followed the rate of ER and HER2 positivity, illustrating the clinical effect of inter- and intra-laboratory variability. There was limited variability among departments in ER, PR, and HER2 testing. However, even a few outlier pathology labs affected endocrine and HER2-targeted treatment rates in a clinically relevant proportion, suggesting the need for improvement. High variability was found in grading and Ki67 assessment, illustrating the need for the adoption of new technologies in practice.
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| 2. |
- Alejandre, Elizabeth M., et al.
(author)
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Characterization Factors to Assess Land Use Impacts on Pollinator Abundance in Life Cycle Assessment
- 2023
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In: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 57:8, s. 3445-3454
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Journal article (peer-reviewed)abstract
- While wild pollinators play a key role in global food production, their assessment is currently missing from the most commonly used environmental impact assessment method, Life Cycle Assessment (LCA). This is mainly due to constraints in data availability and compatibility with LCA inventories. To target this gap, relative pollinator abundance estimates were obtained with the use of a Delphi assessment, during which 25 experts, covering 16 nationalities and 45 countries of expertise, provided scores for low, typical, and high expected abundance associated with 24 land use categories. Based on these estimates, this study presents a set of globally generic characterization factors (CFs) that allows translating land use into relative impacts to wild pollinator abundance. The associated uncertainty of the CFs is presented along with an illustrative case to demonstrate the applicability in LCA studies. The CFs based on estimates that reached consensus during the Delphi assessment are recommended as readily applicable and allow key differences among land use types to be distinguished. The resulting CFs are proposed as the first step for incorporating pollinator impacts in LCA studies, exemplifying the use of expert elicitation methods as a useful tool to fill data gaps that constrain the characterization of key environmental impacts.
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| 3. |
- Axelsson, Lars, et al.
(author)
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Prognostic factors for head and neck cancer of unknown primary including the impact of human papilloma virus infection
- 2017
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In: Journal of Otolaryngology-Head & Neck Surgery. - : Springer Science and Business Media LLC. - 1916-0216. ; 46
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Journal article (peer-reviewed)abstract
- Background: Head and neck cancer of unknown primary (HNCUP) is rare and prospective studies are lacking. The impact of different prognostic factors such as age and N stage is not completely known, the optimal treatment is not yet established, and the reported survival rates vary. In the last decade, human papilloma virus (HPV) has been identified as a common cause of and important prognostic factor in oropharyngeal cancer, and there is now growing interest in the importance of HPV for HNCUP. The aim of the present study on curatively treated HNCUP was to investigate the prognostic importance of different factors, including HPV status, treatment, and overall survival. Methods: A search for HNCUP was performed in the Swedish Cancer Registry, Western health district, between the years 1992-2009. The medical records were reviewed, and only patients with squamous cell carcinoma or undifferentiated carcinoma treated with curative intent were included. The tumor specimens were retrospectively analyzed for HPV with p16 immunostaining. Results: Sixty- eight patients were included. The mean age was 59 years. The majority were males, and had N2 tumors. Sixty-nine percent of the tumors were HPV positive using p16 staining. Patients who were older than 70 years, patients with N3-stage tumors, and patients with tumors that were p16 negative had a significantly worse prognosis. The overall 5-year survival rate for patients with p16-positive tumors was 88% vs 61% for p16- negative tumors. Treatment with neck dissection and postoperative radiation or (chemo) radiation had 81 and 88% 5- year survival rates, respectively. The overall and disease- free 5-year survival rates for all patients in the study were 82 and 74%. Conclusions: Curatively treated HNCUP had good survival. HPV infection was common. Independent prognostic factors for survival were age over 70 years, HPV status and N3 stage. We recommend that HPV analysis should be performed routinely for HNCUP. Treatment with neck dissection and postoperative radiation or (chemo) radiation showed similar survival rates.
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| 4. |
- Barzó, P, et al.
(author)
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[Giant cell interstitial pneumonia]. : Oriássejtes interstitialis pneumonia.
- 1998
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In: Orvosi hetilap. - 0030-6002. ; 139:51, s. 3079-83
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Journal article (peer-reviewed)abstract
- GIP is a rarely occurring disorder. There is only few literature from its first description. Authors observed the course of GIP in the case of a 54 year old female patient in the form of bilateral disseminated microfocal pulmonary shadows, increased reticular outline with associated respiratory insufficiency. Open fine needle pulmonary biopsy proved giant cell desquamative alveolitis with help of light- and electronmicroscopical and histochemical examinations. Although possibility of exogenic, inhalative factor or/and infectious origin arose in causing the disease, disposition from the patient's actual immunological status could had helped the evolution of the disease. This fact seemed to be supported by the histologically proven associated dermatitis purpurica pigmentosa (Schamberg disease). With methylprednisolon therapy full radiological recovery occurred, while Schamberg disease was little influenced by the above mentioned therapy. The patient is pulmonologically symptom-free and without complaint after 1 year without any steroid-medication.
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| 5. |
- Berg, Malin, 1976, et al.
(author)
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Replacement of a Tracheal Stenosis with a Tissue-Engineered Human Trachea Using Autologous Stem Cells: A Case Report
- 2014
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In: Tissue Engineering. Part A. - 1937-3341 .- 1937-335X. ; 20:1-2, s. 389-397
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Journal article (peer-reviewed)abstract
- Cell-based therapies, involving tissue engineering represent interesting and potentially important strategies for treatment of patients with various disorders. Here, using a detergent-enzymatic method we prepared an intact 3-dimensional scaffold of an extracellular matrix (ECM) derived from a human cadaver donor trachea, which we repopulated with autologous stem cells and implanted into a 76-year old patient with tracheal stenosis including lower part of the larynx. Although the graft provided the patient with an open airway, a week after surgery, the mucous membrane of the graft was covered by a 1-2mm thick fungal infection, which was treated with local and systemic anti-fungal therapy. The airway lumen was postoperatively controlled by fiberbrandoscopy and found stable and sufficient. However, twenty-three days later the patient died due to cardiac arrest but with a patent, open, stable tracheal transplant and intact anastomoses. Histopathological results of the transplanted tracheal graft at autopsy showed a squamous but not ciliated epithelium, neovascularization, bundles of -sma positive muscle cells, serous glands and nerve fibres with S-100 positive nerve cells in the submucosa and intact chondrocytes in the cartilage. Our findings suggest that although autologous stem cells- engineered tracheal matrices may represent a tool for clinical tracheal replacement. Further preclinical studies are required for generating functional airway grafts and long term effects of such grafts.
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| 6. |
- Biermann, Jana, et al.
(author)
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A 17-marker panel for global genomic instability in breast cancer.
- 2020
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In: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 112:2, s. 1151-1161
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Journal article (peer-reviewed)abstract
- Genomic instability is a hallmark of cancer that plays a pivotal role in breast cancer development and evolution. A number of existing prognostic gene expression signatures for breast cancer are based on proliferation-related genes. Here, we identified a 17-marker panel associated with genome stability. A total of 136 primary breast carcinomas were stratified by genome stability. Matched gene expression profiles showed an innate segregation based on genome stability. We identified a 17-marker panel stratifying the training and validation cohorts into high- and low-risk patients. The 17 genes associated with genomic instability strongly impacted clinical outcome in breast cancer. Pathway analyses determined chromosome organisation, cell cycle regulation, and RNA processing as the underlying biological processes, thereby offering options for drug development and treatment tailoring. Our work supports the applicability of the 17-marker panel to improve clinical outcome prediction for breast cancer patients based on a signature accounting for genomic instability.
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| 7. |
- Biermann, Jana, et al.
(author)
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Clonal relatedness in tumour pairs of breast cancer patients.
- 2018
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In: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-542X. ; 20:1
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Journal article (peer-reviewed)abstract
- Molecular classification of tumour clonality is currently not evaluated in multiple invasive breast carcinomas, despite evidence suggesting common clonal origins. There is no consensus about which type of data (e.g. copy number, mutation, histology) and especially which statistical method is most suitable to distinguish clonal recurrences from independent primary tumours.Thirty-seven invasive breast tumour pairs were stratified according to laterality and time interval between the diagnoses of the two tumours. In a multi-omics approach, tumour clonality was analysed by integrating clinical characteristics (n=37), DNA copy number (n=37), DNA methylation (n=8), gene expression microarray (n=7), RNA sequencing (n=3), and SNP genotyping data (n=3). Different statistical methods, e.g. the diagnostic similarity index (SI), were used to classify the tumours as clonally related recurrences or independent primary tumours.The SI and hierarchical clustering showed similar tendencies and the highest concordance with the other methods. Concordant evidence for tumour clonality was found in 46% (17/37) of patients. Notably, no association was found between the current clinical guidelines and molecular tumour features.A more accurate classification of clonal relatedness between multiple breast tumours may help to mitigate treatment failure and relapse by integrating tumour-associated molecular features, clinical parameters, and statistical methods. Guidelines need to be defined with exact thresholds to standardise clonality testing in a routine diagnostic setting.
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| 8. |
- Biermann, Jana, et al.
(author)
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Radiation-induced genomic instability in breast carcinomas of the Swedish haemangioma cohort.
- 2019
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In: Genes, chromosomes & cancer. - : Wiley. - 1098-2264 .- 1045-2257. ; 58:9, s. 627-35
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Journal article (peer-reviewed)abstract
- Radiation-induced genomic instability (GI) is hypothesized to persist after exposure and ultimately promote carcinogenesis. Based on the absorbed dose to the breast, an increased risk of developing breast cancer was shown in the Swedish haemangioma cohort that was treated with radium-226 for skin haemangioma as infants. Here, we screened 31 primary breast carcinomas for genetic alterations using the OncoScan CNV Plus Assay to assess GI and chromothripsis-like patterns associated with the absorbed dose to the breast. Higher absorbed doses were associated with increased numbers of copy number alterations (CNAs) in the tumour genome and thus a more unstable genome. Hence, the observed dose-dependent GI in the tumour genome is a measurable manifestation of the long-term effects of irradiation. We developed a highly predictive Cox regression model for overall survival based on the interaction between absorbed dose and GI. The Swedish haemangioma cohort is a valuable cohort to investigate the biological relationship between absorbed dose and GI in irradiated humans. This work gives a biological basis for improved risk assessment to minimize carcinogenesis as a secondary disease after radiation therapy. This article is protected by copyright. All rights reserved.
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| 9. |
- Biermann, Jana, et al.
(author)
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Tumour clonality in paired invasive breast carcinomas
- 2019
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In: Cancer Research. - 0008-5472.
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Conference paper (other academic/artistic)abstract
- Background: Multiple invasive breast tumours may represent either independent primary tumours or clonal recurrences of the first tumour, where the same progenitor cell gives rise to all of the detected tumours. Consequently, the driver events for the progenitor cell need to have been identical in early tumour development. Molecular classification of tumour clonality is not currently evaluated in multiple invasive breast carcinomas, despite evidence suggesting common clonal origins. Furthermore, there is no consensus about which type of biological data (e.g. copy number, mutation, histology) and especially which statistical method is most suitable to distinguish clonal recurrences from independent primary tumours. Methods: Thirty-seven invasive breast tumour pairs were stratified by laterality (bilateral vs. ipsilateral) and the time interval between the diagnoses of the first and second tumours (synchronous vs. metachronous). Both tumours from the same patient were analysed by integrating clinical characteristics (n = 37), DNA copy number (n = 37), DNA methylation (n = 8), gene expression microarray (n = 7), RNA sequencing (n = 3), and SNP genotyping data (n = 3). Different statistical methods, e.g. the diagnostic similarity index (SI), distance measure, shared segment analysis etc., were used to classify the tumours from the same patient as clonally related recurrences or independent primary tumours. Results: The SI applied on DNA copy numbers derived from aCGH (array comparative genomic hybridization) data was determined as the strongest indicator of clonal relatedness as it showed the highest concordance with all other methods. The distance measure was the most conservative method and the shared segment analysis most liberal. Concordant evidence for tumour clonality was found in 46% (17/37) of the patients. Notably, no significant association was found between the clinical characteristics and molecular tumour features. Conclusions: A more accurate classification of clonal relatedness between multiple breast tumours may help to mitigate treatment failure and relapse by integrating tumour-associated molecular features, clinical parameters, and statistical methods. In cases of extremely similar or different tumour pairs, the results showed consistency regardless of the method used. The SI can be easily integrated into clinical routine using FFPE samples to obtain copy number data. However, clinical guidelines with exact thresholds need to be defined to standardize clonality testing in a routine diagnostic setting.
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| 10. |
- Chin, Kian, et al.
(author)
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Tumor-infiltrating lymphocytes as a predictor of axillary and primary tumor pathological response after neoadjuvant chemotherapy in patients with breast cancer: a retrospective cohort study.
- 2024
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In: Breast Cancer Research and Treatment. - : SPRINGER. - 0167-6806 .- 1573-7217. ; 207:1, s. 49-63
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Journal article (peer-reviewed)abstract
- Tumor-infiltrating lymphocytes (TILs) can predict complete pathological response (pCR) of tumor in the breast but not so well-defined in the axilla after neoadjuvant chemotherapy. Since axillary surgery is being increasingly de-escalated after NACT, we aimed to investigate the relationship between TILs and pCR in the axilla and breast, as well as survival amongst NACT patients.Clinicopathological data on patients who underwent NACT between 2013 and 2020 were retrospectively examined. Specifically, pre-TILs (before NACT), post-TILs (after NACT) and ΔTIL (changes in TILs) were assessed. Primary endpoint was pCR and secondary endpoints were breast cancer-free interval (BCFI) and overall survival (OS).Two hundred and twenty patients with nodal metastases were included. Overall axillary and breast pCR rates were 42.7% (94/220) and 39.1% (86/220), respectively, whereas the combined pCR rate was 32.7% (72/220). High pre-TILs (OR 2.03, 95% CI 1.02-4.05; p=0.04) predicted axillary pCR whereas, high post-TILs (OR 0.33, 95% CI 0.14-0.76; p=0.009) and increased ΔTILs (OR 0.25, 95% CI 0.08-0.79; p=0.02) predicted non-axillary pCR. TILs were not a significant predictor for BCFI and OS.This study supports the potential use of pre-TILs to select initially node-positive patients for axillary surgical de-escalation after NACT.
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| 11. |
- Chin, Kian, et al.
(author)
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Tumor-infiltrating lymphocytes as a predictor of axillary and primary tumor pathological response after neoadjuvant chemotherapy in patients with breast cancer: a retrospective cohort study
- 2024
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In: Breast Cancer Research and Treatment. - : SPRINGER. - 0167-6806 .- 1573-7217.
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Journal article (peer-reviewed)abstract
- Purpose Tumor-infiltrating lymphocytes (TILs) can predict complete pathological response (pCR) of tumor in the breast but not so well-defined in the axilla after neoadjuvant chemotherapy. Since axillary surgery is being increasingly de-escalated after NACT, we aimed to investigate the relationship between TILs and pCR in the axilla and breast, as well as survival amongst NACT patients.Methods Clinicopathological data on patients who underwent NACT between 2013 and 2020 were retrospectively examined. Specifically, pre-TILs (before NACT), post-TILs (after NACT) and Delta TIL (changes in TILs) were assessed. Primary endpoint was pCR and secondary endpoints were breast cancer-free interval (BCFI) and overall survival (OS).Results Two hundred and twenty patients with nodal metastases were included. Overall axillary and breast pCR rates were 42.7% (94/220) and 39.1% (86/220), respectively, whereas the combined pCR rate was 32.7% (72/220). High pre-TILs (OR 2.03, 95% CI 1.02-4.05; p = 0.04) predicted axillary pCR whereas, high post-TILs (OR 0.33, 95% CI 0.14-0.76; p = 0.009) and increased Delta TILs (OR 0.25, 95% CI 0.08-0.79; p = 0.02) predicted non-axillary pCR. TILs were not a significant predictor for BCFI and OS.Conclusions This study supports the potential use of pre-TILs to select initially node-positive patients for axillary surgical de-escalation after NACT.
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| 12. |
- Cole, Lorna J., et al.
(author)
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A critical analysis of the potential for EU Common Agricultural Policy measures to support wild pollinators on farmland
- 2020
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In: Journal of Applied Ecology. - : Wiley. - 0021-8901 .- 1365-2664. ; 57:4, s. 681-694
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Journal article (peer-reviewed)abstract
- Agricultural intensification and associated loss of high-quality habitats are key drivers of insect pollinator declines. With the aim of decreasing the environmental impact of agriculture, the 2014 EU Common Agricultural Policy (CAP) defined a set of habitat and landscape features (Ecological Focus Areas: EFAs) farmers could select from as a requirement to receive basic farm payments. To inform the post-2020 CAP, we performed a European-scale evaluation to determine how different EFA options vary in their potential to support insect pollinators under standard and pollinator-friendly management, as well as the extent of farmer uptake. A structured Delphi elicitation process engaged 22 experts from 18 European countries to evaluate EFAs options. By considering life cycle requirements of key pollinating taxa (i.e. bumble bees, solitary bees and hoverflies), each option was evaluated for its potential to provide forage, bee nesting sites and hoverfly larval resources. EFA options varied substantially in the resources they were perceived to provide and their effectiveness varied geographically and temporally. For example, field margins provide relatively good forage throughout the season in Southern and Eastern Europe but lacked early-season forage in Northern and Western Europe. Under standard management, no single EFA option achieved high scores across resource categories and a scarcity of late season forage was perceived. Experts identified substantial opportunities to improve habitat quality by adopting pollinator-friendly management. Improving management alone was, however, unlikely to ensure that all pollinator resource requirements were met. Our analyses suggest that a combination of poor management, differences in the inherent pollinator habitat quality and uptake bias towards catch crops and nitrogen-fixing crops severely limit the potential of EFAs to support pollinators in European agricultural landscapes. Policy Implications. To conserve pollinators and help protect pollination services, our expert elicitation highlights the need to create a variety of interconnected, well-managed habitats that complement each other in the resources they offer. To achieve this the Common Agricultural Policy post-2020 should take a holistic view to implementation that integrates the different delivery vehicles aimed at protecting biodiversity (e.g. enhanced conditionality, eco-schemes and agri-environment and climate measures). To improve habitat quality we recommend an effective monitoring framework with target-orientated indicators and to facilitate the spatial targeting of options collaboration between land managers should be incentivised.
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| 13. |
- De Lara, Shahin, et al.
(author)
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GATA3 as a putative marker of breast cancer metastasis-A retrospective immunohistochemical study.
- 2018
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In: The breast journal. - : Hindawi Limited. - 1524-4741 .- 1075-122X. ; 24:2, s. 184-188
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Journal article (peer-reviewed)abstract
- Diagnostic verification of breast cancer metastasis with histopathology and imaging analysis is essential to determine tumor staging. The aim of this study was to validate the utility of GATA3 immunohistochemistry as a diagnostic marker for breast cancer metastases and metastases of unknown primary origin. Retrospective immunohistochemical analysis of GATA3 expression in 164 breast cancer metastases diagnosed between 2004 and 2014 showed a striking difference between mammaglobin and GATA3 expression (51.2% vs 94% positivity). These findings highlight GATA3 as a more reliable and sensitive diagnostic marker for breast cancer metastases and possibly metastatic tumors of unknown origin than mammaglobin.
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| 14. |
- De Lara, Shahin, 1966, et al.
(author)
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The prognostic relevance of FOXA1 and Nestin expression in breast cancer metastases: a retrospective study of 164 cases during a 10-year period (2004-2014)
- 2019
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In: Bmc Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 19
-
Journal article (peer-reviewed)abstract
- BackgroundCurrent prognostic markers cannot adequately predict the clinical outcome of breast cancer patients. Therefore, additional biomarkers need to be included in routine immune panels. FOXA1 was a significant predictor of favorable outcome in primary breast cancer, while Nestin expression is preferentially found in triple-negative tumors with increased rate of nodal metastases, and reduced survival. No studies have investigated the prognostic value of FOXA1 and Nestin expression in breast cancer metastases.MethodsBreast cancer metastases (n=164) from various anatomical sites were retrospectively analyzed by immunohistochemistry for FOXA1, Nestin and GATA3 expression. Cox regression analysis assessed the prognostic value of FOXA1 and Nestin expression.ResultsIn breast cancer metastases, FOXA1 expression was associated with Nestin-negativity, GATA3-positivity, ER-positivity, HER2-positivity and non-triple-negative status (P<0.05). In contrast, Nestin expression was associated with FOXA1-negative, GATA3-negative, ER-negative, and triple-negative metastases (P<0.05). Univariate Cox regression analysis showed FOXA1 expression was predictive of overall survival (OS, P=0.00048) and metastasis-free survival (DMFS, P=0.0011), as well as, distant metastasis-free survival in ER-positive patients (P=0.036) and overall survival in ER-negative patients (P=0.024). Multivariate analysis confirmed the significance of FOXA1 for both survival endpoints in metastatic breast cancer patients (OS, P=0.0033; DMFS, P=0.015).ConclusionsIn our study, FOXA1 was expressed mostly in ER-positive breast cancer metastases. Expression of Nestin was related to triple-negative metastases, where brain was the most frequent metastatic site. These findings highlight the clinical utility of FOXA1 and Nestin expression and warrant their inclusion in routine immunohistochemical panels for breast carcinoma.
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| 15. |
- Ekroos, Johan, et al.
(author)
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High land-use intensity in grasslands constrains wild bee species richness in Europe
- 2020
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In: Biological Conservation. - : Elsevier BV. - 0006-3207. ; 241
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Journal article (peer-reviewed)abstract
- There is widespread concern regarding declines in bee populations given their importance for the functioning of both natural and managed ecosystems. An increasing number of studies find negative relations between bee species richness and simplification of agricultural landscapes, but the role of land-use intensity and its relative importance compared to landscape simplification remain less clear. We compared the relative effects of nitrogen inputs, as a proxy for land-use intensity, and proportion of natural and semi-natural habitat, as a measure of landscape complexity on total bee species richness, rare species richness and dominant crop-visiting species richness. We used data from 282 grasslands across five countries, covering the entire range of low intensity, no-input systems, to high-input sites (>400 kg N/ha/year). We found consistent negative impacts of increasing land-use intensity at a regional scale on total bee species richness and dominant crop-visiting species across Europe, but no such effects of landscape complexity. In contrast, the richness of rare bee species was not significantly related to increasing land-use intensity. Nevertheless, based on species accumulation curves, grasslands with no nitrogen inputs had higher total bee richness and higher shares of rare species compared with sites with high nitrogen inputs (>125 kg N/ha/year). Our results highlight the importance of retaining grasslands characterised by low land-use intensity across agricultural landscapes to promote bee diversity.
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| 16. |
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| 17. |
- Engqvist, Hanna, 1985, et al.
(author)
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Immunohistochemical validation of COL3A1, GPR158 and PITHD1 as prognostic biomarkers in early-stage ovarian carcinomasn
- 2019
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 19:1
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Journal article (peer-reviewed)abstract
- Background: Ovarian cancer is the main cause of gynecological cancer-associated death. However, 5- Methods: Here, we evaluated the prognostic role of 29 genes for early-stage (I and II) ovarian Results: We provide evidence of aberrant protein expression patterns for Collagen type III alpha 1 Conclusions: The novel biomarkers identified here may improve prognostication at the time of
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| 18. |
- Engqvist, Hanna, 1985, et al.
(author)
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Integrative genomics approach identifies molecular features associated with early-stage ovarian carcinoma histotypes.
- 2020
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- Ovarian cancer comprises multiple subtypes (clear-cell (CCC), endometrioid (EC), high-grade serous (HGSC), low-grade serous (LGSC), and mucinous carcinomas (MC)) with differing molecular and clinical behavior. However, robust histotype-specific biomarkers for clinical use have yet to be identified. Here, we utilized a multi-omics approach to identify novel histotype-specific genetic markers associated with ovarian carcinoma histotypes (CCC, EC, HGSC, and MC) using DNA methylation, DNA copy number alteration and RNA sequencing data for 96 primary invasive early-stage (stage I and II) ovarian carcinomas. More specifically, the DNA methylation analysis revealed hypermethylation for CCC in comparison with the other histotypes. Moreover, copy number imbalances and novel chromothripsis-like rearrangements (n=64) were identified in ovarian carcinoma, with the highest number of chromothripsis-like patterns in HGSC. For the 1000 most variable transcripts, underexpression was most prominent for all histotypes in comparison with normal ovarian samples. Overall, the integrative approach identified 46 putative oncogenes (overexpressed, hypomethylated and DNA gain) and three putative tumor suppressor genes (underexpressed, hypermethylated and DNA loss) when comparing the different histotypes. In conclusion, the current study provides novel insights into molecular features associated with early-stage ovarian carcinoma that may improve patient stratification and subclassification of the histotypes.
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| 19. |
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| 20. |
- Eros, Nora, et al.
(author)
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Large B-cell lymphoma of the leg in a patient with multiple malignant tumours.
- 2003
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In: Acta dermato-venereologica. - : Medical Journals Sweden AB. - 0001-5555. ; 83:5, s. 354-7
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Journal article (peer-reviewed)abstract
- A patient who had primary gastric B-cell non-Hodgkin's lymphoma, invasive ductal breast cancer and a basocellular carcinoma of the forehead in her medical history was studied. Three years after polychemotherapy and irradiation of the breast cancer, a rapidly enlarging, ulcerated violaceous tumour developed on the patient's left leg. The tumour was identified by the histopathological, immunohistochemical and immunoglobulin gene rearrangement analyses as a cutaneous large B-cell lymphoma. No signs of extracutaneous involvement were detectable. Despite surgical excision, interferon-alpha2b treatment and chlorambucil + prednisone chemotherapy, a relapse occurred in the previously affected site, whereafter the patient received radiotherapy. She was lost to follow-up, and died approximately 14 months after the surgical intervention without autopsy. We discuss the clinical and histologic features and outcome of the large B-cell lymphoma of the leg, its coincidence with other diseases, and the uncommon occurrence of primary multiple malignant tumours.
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| 21. |
- Erós, N, et al.
(author)
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[New aspects in the classification of cutaneous lymphomas]. : Szemléletváltozás a kután lymphomák klasszifikációjában.
- 2001
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In: Orvosi hetilap. - 0030-6002. ; 142:8, s. 393-8
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Journal article (peer-reviewed)abstract
- Authors discuss the classification of primary cutaneous lymphomas created by the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer (EORTC) in 1996, which is based on the clinical, histological, immunohistochemical and genetic features of cutaneous lymphomas. Unlike the previous histologic classifications it contains well-defined disease entities characterized by their clinical and histological picture, clinical outcome, behaviour and therapeutic response. This classification does not use the term of low grade or high grade lymphoma, but introduces the indolent, aggressive and provisional subgroups in the T-cell lymphomas, and indolent, intermediate and provisional subgroups in the B-cell group. Authors demonstrate the EORTC classification by their own cases calling the attention to the clinical and therapeutic difference between nodal and extranodal lymphomas, and discuss the up-to-date therapeutic possibilities.
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| 22. |
- Erös, N, et al.
(author)
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Successful treatment of transient acantholytic dermatosis with systemic steroids.
- 1998
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In: The Journal of dermatology. - 0385-2407. ; 25:7, s. 469-75
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Journal article (peer-reviewed)abstract
- A sixty-year-old man, developed 2-5 mm sized, hyperemic, itchy papules, vesicles, erosions and crusts on hyperemic base on his chest, abdomen, back, gluteal region, and proximal sites of his upper and lower extremities. The direct and indirect immunoflurescence tests were negative. Histology revealed extensive acantholysis in the epidermis in the following forms: pemphigus vulgaris-like suprabasal acantholysis, Darier-like acantholytic dyskeratosis with corps ronds, Hailey-Hailey-like suprabasal clefts, and pemphigus foliaceus-like superficial acantholysis with spongiosis. Using systemic steroids, topical drying, and reepithelising therapy, the patient was cured. He was symptom-free the first, fourth, and thirteenth months after finishing steroid therapy. We review the literature and the new subdivision of the disease according to the histological and clinical features.
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| 23. |
- Fehr, Andre, et al.
(author)
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The MYB-NFIB gene fusion-a novel genetic link between adenoid cystic carcinoma and dermal cylindroma
- 2011
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In: The Journal of Pathology. - : Wiley. - 1096-9896 .- 0022-3417. ; 224:3, s. 322-7
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Journal article (peer-reviewed)abstract
- We have recently shown that the recurrent t(6;9)(q22 approximately 23;p23 approximately 24) translocation in adenoid cystic carcinoma (ACC) of the breast and head and neck results in a fusion of the two transcription factor genes MYB and NFIB. Here we demonstrate, for the first time, that benign sporadic, dermal cylindromas also express the MYB-NFIB gene fusion. RT-PCR and immunohistochemical analyses revealed that eight of 12 analysed tumours (67%) expressed MYB-NFIB fusion transcripts and/or stained positive for MYB protein. Nucleotide sequence analyses confirmed that the composition of the chimeric transcript variants identified was identical to that in ACC, suggesting a similar molecular mechanism of activation of MYB in cylindroma as in ACC. In contrast, no evidence for the presence of the MYB-NFIB fusion was found in other types of basaloid skin and salivary gland tumours, indicating that the fusion indeed has a restricted expression pattern. Our findings broaden the spectrum of neoplasms associated with MYB oncogene activation and reveal a novel genetic link between ACC and dermal cylindroma. These results, together with our previous observations, further strengthen the evidence for common molecular pathways of importance for the development of both benign and malignant breast, salivary and adnexal tumours.
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| 24. |
- Gagic, Vesna, et al.
(author)
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Combined effects of agrochemicals and ecosystem services on crop yield across Europe
- 2017
-
In: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 20:11, s. 1427-1436
-
Journal article (peer-reviewed)abstract
- Simultaneously enhancing ecosystem services provided by biodiversity below and above ground is recommended to reduce dependence on chemical pesticides and mineral fertilisers in agriculture. However, consequences for crop yield have been poorly evaluated. Above ground, increased landscape complexity is assumed to enhance biological pest control, whereas below ground, soil organic carbon is a proxy for several yield-supporting services. In a field experiment replicated in 114 fields across Europe, we found that fertilisation had the strongest positive effect on yield, but hindered simultaneous harnessing of below- and above-ground ecosystem services. We furthermore show that enhancing natural enemies and pest control through increasing landscape complexity can prove disappointing in fields with low soil services or in intensively cropped regions. Thus, understanding ecological interdependences between land use, ecosystem services and yield is necessary to promote more environmentally friendly farming by identifying situations where ecosystem services are maximised and agrochemical inputs can be reduced.
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| 25. |
- Garratt, Michael P D, et al.
(author)
-
Opportunities to reduce pollination deficits and address production shortfalls in an important insect pollinated crop
- 2021
-
In: Ecological Applications. - : Wiley. - 1051-0761 .- 1939-5582.
-
Journal article (peer-reviewed)abstract
- Pollinators face multiple pressures and there is evidence of populations in decline. As demand for insect-pollinated crops increases, crop production is threatened by shortfalls in pollination services. Understanding the extent of current yield deficits due to pollination and identifying opportunities to protect or improve crop yield and quality through pollination management is therefore of international importance. To explore the extent of 'pollination deficits', where maximum yield is not being achieved due to insufficient pollination, we use an extensive dataset on a globally important crop, apples. We quantified how these deficits vary between orchards and countries as well as compare 'pollinator dependence' across different apple varieties. We found evidence of pollination deficits and in some cases, risks of over-pollination were even apparent where fruit quality could be reduced by too much pollination. In almost all regions studied we found some orchards performing significantly better than others, in terms of avoiding a pollination deficit and crop yield shortfalls due to sub-optimal pollination. This represents an opportunity to improve production through better pollinator and crop management. Our findings also demonstrate that pollinator dependence varies considerably between apple varieties in terms of fruit number and fruit quality. We propose that assessments of pollination service and deficits in crops can be used to quantify supply and demand for pollinators and help target local management to address deficits although crop variety has a strong influence on the role of pollinators.
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| 26. |
- Herbertsson, Lina, et al.
(author)
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Bees increase seed set of wild plants while the proportion of arable land has a variable effect on pollination in European agricultural landscapes
- 2021
-
In: Plant Ecology and Evolution. - : Societe Royale de Botanique de Belgique. - 2032-3913 .- 2032-3921. ; 154:3, s. 341-350
-
Journal article (peer-reviewed)abstract
- Background and aims: Agricultural intensification and loss of farmland heterogeneity have contributed to population declines of wild bees and other pollinators, which may have caused subsequent declines in insect-pollinated wild plants.Material and methods: Using data from 37 studies on 22 pollinator-dependent wild plant species across Europe, we investigated whether flower visitation and seed set of insect-pollinated plants decline with an increasing proportion of arable land within 1 km.Key results: Seed set increased with increasing flower visitation by bees, most of which were wild bees, but not with increasing flower visitation by other insects. Increasing proportion of arable land had a strongly variable effect on seed set and flower visitation by bees across studies.Conclusion:Factors such as landscape configuration, local habitat quality, and temporally changing resource availability (e.g. due to mass-flowering crops or honey bee hives) could have modified the effect of arable land on pollination. While our results highlight that the persistence of wild bees is crucial to maintain plant diversity, we also show that pollen limitation due to declining bee populations in homogenized agricultural landscapes is not a universal driver causing parallel losses of bees and insect-pollinated plants.
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| 27. |
- Hultborn, Ragnar, 1946, et al.
(author)
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Male Breast Carcinoma after Irradiation and Long-Term Phenothiazine Exposure : A Case Report
- 2020
-
In: Case Reports in Oncology. - : S. Karger AG. - 1662-6575. ; 13:2, s. 956-961
-
Journal article (peer-reviewed)abstract
- We present a young male patient with breast cancer having several risk factors likely acting in consort: irradiation of the breast for gynecomastia in adolescence and a life-long administration of phenothiazine for schizophrenia from the age of 16 years, with elevated serum prolactin level resulting in breast cancer development 24 years after irradiation.
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| 28. |
- Hutchinson, Louise A., et al.
(author)
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Using ecological and field survey data to establish a national list of the wild bee pollinators of crops
- 2021
-
In: Agriculture, Ecosystems and Environment. - : Elsevier BV. - 0167-8809 .- 1873-2305. ; 315
-
Journal article (peer-reviewed)abstract
- The importance of wild bees for crop pollination is well established, but less is known about which species contribute to service delivery to inform agricultural management, monitoring and conservation. Using sites in Great Britain as a case study, we use a novel qualitative approach combining ecological information and field survey data to establish a national list of crop pollinating bees for four economically important crops (apple, field bean, oilseed rape and strawberry). A traits data base was used to establish potential pollinators, and combined with field data to identify both dominant crop flower visiting bee species and other species that could be important crop pollinators, but which are not presently sampled in large numbers on crops flowers. Whilst we found evidence that a small number of common, generalist species make a disproportionate contribution to flower visits, many more species were identified as potential pollinators, including rare and specialist species. Furthermore, we found evidence of substantial variation in the bee communities of different crops. Establishing a national list of crop pollinators is important for practitioners and policy makers, allowing targeted management approaches for improved ecosystem services, conservation and species monitoring. Data can be used to make recommendations about how pollinator diversity could be promoted in agricultural landscapes. Our results suggest agri-environment schemes need to support a higher diversity of species than at present, notably of solitary bees. Management would also benefit from targeting specific species to enhance crop pollination services to particular crops. Whilst our study is focused upon Great Britain, our methodology can easily be applied to other countries, crops and groups of pollinating insects.
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| 29. |
- Janeva, Slavica, et al.
(author)
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Adjuvant chemotherapy and survival in women aged 70 years and older with triple-negative breast cancer: a Swedish population-based propensity score-matched analysis
- 2020
-
In: The Lancet Healthy Longevity. - 2666-7568. ; 1:3
-
Journal article (peer-reviewed)abstract
- Background: Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer associated with poor survival, in which adjuvant systemic treatments are limited to chemotherapy. Due to competing mortality risks and comorbidities, older patients with TNBC are often undertreated with adjuvant chemotherapy, and clinical trials on this problem are scarce, despite a growing patient population. This study aimed to assess outcomes for patients aged 70 years and older with TNBC with or without chemotherapy in a national population-based registry, to provide information that can assist in treatment decisions for these patients. Methods: In this population-based registry study, data on all patients aged 70 years and older diagnosed with primary early TNBC (larger than 5 mm in diameter and without distant metastasis) and surgically treated between Jan 1, 2009, and Dec 31, 2016, were retrieved from the Swedish National Breast Cancer Register, the Swedish Patient Register, and the Swedish Cause of Death Register. Patients with incomplete data (on oestrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2 status, surgical procedure in the breast, or information about chemotherapy) were excluded. A propensity score-matched (PSM) model was used to examine the outcomes of adjuvant chemotherapy on 5-year breast cancer-specific survival (BCSS) and 5-year overall survival (OS), adjusted for age, tumour size, tumour grade, nodal status, and comorbidities. Findings: Of 1130 women eligible for analysis, 368 (32·6%) received adjuvant chemotherapy, 45 (4·0%) received neoadjuvant treatment, and 717 (63·5%) did not receive chemotherapy. 5-year BCSS was significantly improved in patients who received adjuvant chemotherapy (85% [95% CI 81–89]) compared with patients who did not receive chemotherapy (68% [64–72]; p<0·0001). A similar benefit was observed in 5-year OS (79% [95% CI 75–84] vs 49% [45–53]; p<0·0001). In our PSM analysis, 5-year BCSS in patients treated with adjuvant chemotherapy was 83% (95% CI 78–89), versus 73% (67–80; p=0·014) in patients not treated with chemotherapy. 5-year OS in patients treated with adjuvant chemotherapy was 75% (95% CI 69–82), versus 63% (57–71; p=0·029) in patients who did not receive chemotherapy. Interpretation: In this PSM registry analysis of surgically treated female patients aged 70 years and older with TNBC without distant metastasis, we identified a significant benefit both in 5-year BCSS and 5-year OS with adjuvant chemotherapy versus no chemotherapy, which persisted when adjusting for age and comorbidities. These results underline the importance of considering adjuvant chemotherapy in older patients. Funding: Knut and Alice Wallenberg Foundation, Assar Gabrielsson Foundation.
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| 30. |
- Janeva, Slavica, et al.
(author)
-
Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) - Case Report
- 2020
-
In: Annals of Clinical and Medical Case Reports. - 2639-8109. ; 3:3, s. 1-6
-
Research review (peer-reviewed)abstract
- Demand for aesthetic breast surgery is increasing worldwide, both for cosmetic reasons and postop- erative breast reconstruction for breast cancer patients. Although the number of women with breast prostheses is steadily increasing, incidence rates for breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) are low, with an estimated incidence of 0.1-0.3 per 100,000 women with prostheses annually. Common clinical presentation of BIA-ALCL may include breast asymmetry, palpable mass, late seroma, local pain, and firmness. However, cytological examination of seroma fluid may reveal the condition, which should be followed by implant removal and total capsulectomy. In the majority of cases, capsulectomy is curative. Preoperative information about the risk of developing BIA-ALCL is recommended for patients with breast implants. Here, we report two BIA-ALCL cases, where one case was diagnosed after breast cosmetic surgery and the other patient had undergone breast reconstructive surgery with implants after breast cancer treatment.
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| 31. |
- Janeva, Slavica, et al.
(author)
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Clinical evaluation of molecular surrogate subtypes in patients with ipsilateral multifocal primary breast cancer
- 2023
-
In: Breast Cancer Research. - 1465-5411. ; 25:1
-
Journal article (peer-reviewed)abstract
- BackgroundWhen ipsilateral multifocal primary breast cancer (IMBC) is detected, standard routine is to evaluate the largest tumor with immunohistochemistry (IHC). As all foci are not routinely characterized, many patients may not receive optimal adjuvant treatment. Here, we assess the clinical relevance of examining at least two foci present in patients with IMBC.MethodsPatients diagnosed and treated for IMBC at Sahlgrenska University Hospital (Gothenburg, Sweden) between 2012 and 2017 were screened. In total, 180 patients with >= 2 invasive foci (183 specimens) were assessed with IHC and included in this study. Expression of the estrogen (ER) and progesterone (PR) receptors, Ki67, HER2, and tumor grade were used to determine the molecular surrogate subtypes and discordance among the foci was recorded. An additional multidisciplinary team board was then held to re-assess whether treatment recommendations changed due to discordances in molecular surrogate subtype between the different foci.ResultsDiscordance in ER, PR, HER2, and Ki67 was found in 2.7%, 19.1%, 7.7%, and 16.9% of invasive foci, respectively. Discordance in the molecular surrogate subtypes was found in 48 of 180 (26.7%) patients, which resulted in therapy changes for 11 patients (6.1%). These patients received additional endocrine therapy (n = 2), chemotherapy (n = 3), and combined chemotherapy and trastuzumab (n = 6).ConclusionTaken together, when assessing at least two tumor foci with IHC, regardless of shared morphology or tumor grade between the different foci, 6.1% of patients with IMBC were recommended additional adjuvant treatment. A pathologic assessment using IHC of all foci is therefore recommended to assist in individualized treatment decision making.
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| 32. |
- Janeva, Slavica, et al.
(author)
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Clinical relevance of biomarker discordance between primary breast cancers and synchronous axillary lymph node metastases.
- 2023
-
In: Clinical & experimental metastasis. - 0262-0898 .- 1573-7276. ; 40:4, s. 299-308
-
Journal article (peer-reviewed)abstract
- Clinical decision-making for patients with breast cancer (BC) is still primarily based on biomarker characteristics of the primary tumor, together with the evaluation of synchronous axillary lymph node metastasis (LNM). In this study, we investigated the prevalence of discordance in the biomarkers and surrogate subtyping between the primary BC and the LNM, and whether subsequent changes would have altered clinical treatment recommendations. In this retrospective study, 94 patients treated for unifocal primary BC and synchronous LNM at Sahlgrenska UniversityHospital during 2018 were included. Estrogen (ER) and progesterone (PR) receptor, Ki67, and HER2 status were assessed in the primary tumor and LNM using immunohistochemistry. Discordances between the primary tumor and the LNM were analyzed for each individual biomarker and surrogate subtyping. The concordance between the primary tumor and the LNM for ER, PR, Ki67, and HER2 status was 98.9%, 89.4%, 72.3%, and 95.8%, respectively. Discordance in surrogate subtyping was found in 28.7% of the tumors and matched LNMs, the majority (81.5%) of which changed to a more favorable subtype in the LNM; most commonly from Luminal B to Luminal A (48.6%). No changes in surrogate subtyping were detected where ER or HER2 status changed from negativity in the BC to positivity in the LNM, thereby showing no additional value in performing immunohistochemistry on the LNM from a treatment decision-making perspective. However, large studies need to be performed that test both the primary BCs and synchronous LNMs for more accurate diagnostics.
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| 33. |
- Johansson, Henrik J., et al.
(author)
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Retinoic acid receptor alpha is associated with tamoxifen resistance in breast cancer
- 2013
-
In: Nature Communications. - : Nature Publishing Group: Nature Communications. - 2041-1723. ; 4:3175
-
Journal article (peer-reviewed)abstract
- About one-third of oestrogen receptor alpha-positive breast cancer patients treated with tamoxifen relapse. Here we identify the nuclear receptor retinoic acid receptor alpha as a marker of tamoxifen resistance. Using quantitative mass spectrometry-based proteomics, we show that retinoic acid receptor alpha protein networks and levels differ in a tamoxifen-sensitive (MCF7) and a tamoxifen-resistant (LCC2) cell line. High intratumoural retinoic acid receptor alpha protein levels also correlate with reduced relapse-free survival in oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen solely. A similar retinoic acid receptor alpha expression pattern is seen in a comparable independent patient cohort. An oestrogen receptor alpha and retinoic acid receptor alpha ligand screening reveals that tamoxifen-resistant LCC2 cells have increased sensitivity to retinoic acid receptor alpha ligands and are less sensitive to oestrogen receptor alpha ligands compared with MCF7 cells. Our data indicate that retinoic acid receptor alpha may be a novel therapeutic target and a predictive factor for oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen.
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| 34. |
- Karlsson, Per, 1963, et al.
(author)
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Patterns and risk factors for locoregional failures after mastectomy for breast cancer: an International Breast Cancer Study Group report
- 2012
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 23:11, s. 2852-2858
-
Journal article (peer-reviewed)abstract
- Rates and risk factors of local, axillary and supraclavicular recurrences can guide patient selection and target for postmastectomy radiotherapy (PMRT). Local, axillary and supraclavicular recurrences were evaluated in 8106 patients enrolled in 13 randomized trials. Patients received chemotherapy and/or endocrine therapy and mastectomy without radiotherapy. Median follow-up was 15.2 years. Ten-year cumulative incidence for chest wall recurrence of > 15% was seen in patients aged < 40 years (16.1%), with >= 4 positive nodes (16.5%) or 0-7 uninvolved nodes (15.1%); for supraclavicular failures > 10%: >= 4 positive nodes (10.2%); for axillary failures of > 5%: aged < 40 years (5.1%), unknown primary tumor size (5.2%), 0-7 uninvolved nodes (5.2%). In patients with 1-3 positive nodes, 10-year cumulative incidence for chest wall recurrence of > 15% were age < 40, peritumoral vessel invasion or 0-7 uninvolved nodes. Age, number of positive nodes and number of uninvolved nodes were significant parameters for each locoregional relapse site. PMRT to the chest wall and supraclavicular fossa is supported in patients with >= 4 positive nodes. With 1-3 positive nodes, chest wall PMRT may be considered in patients aged < 40 years, with 0-7 uninvolved nodes or with vascular invasion. The findings do not support PMRT to the dissected axilla.
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| 35. |
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| 36. |
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| 37. |
- Kimbung, Siker, et al.
(author)
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Contrasting breast cancer molecular subtypes across serial tumor progression stages: biological and prognostic implications.
- 2015
-
In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:32, s. 33306-18
-
Journal article (peer-reviewed)abstract
- The relevance of the intrinsic subtypes for clinical management of metastatic breast cancer is not comprehensively established. We aimed to evaluate the prevalence and prognostic significance of drifts in tumor molecular subtypes during breast cancer progression. A well-annotated cohort of 304 women with advanced breast cancer was studied. Tissue microarrays of primary tumors and synchronous lymph node metastases were constructed. Conventional biomarkers were centrally assessed and molecular subtypes were assigned following the 2013 St Gallen guidelines. Fine-needle aspirates of asynchronous metastases were transcriptionally profiled and subtyped using PAM50. Discordant expression of individual biomarkers and molecular subtypes was observed during tumor progression. Primary luminal-like tumors were relatively unstable, frequently adopting a more aggressive subtype in the metastases. Notably, loss of ER expression and a luminal to non-luminal subtype conversion was associated with an inferior post-recurrence survival. In addition, ER and molecular subtype assessed at all tumor progression stages were independent prognostic factors for post-recurrence breast cancer mortality in multivariable analyses. Our results demonstrate that drifts in tumor molecular subtypes may occur during tumor progression, conferring adverse consequences on outcome following breast cancer relapse.
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| 38. |
- Kovács, Anikó, 1961, et al.
(author)
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ALK-Positive Inflammatory Myofibroblastic Tumor of the Nipple During Pregnancy-An Unusual Presentation of a Rare Disease.
- 2015
-
In: The breast journal. - : Hindawi Limited. - 1524-4741 .- 1075-122X. ; 21:3, s. 297-302
-
Journal article (peer-reviewed)abstract
- Inflammatory myofibroblastic tumors (IMT) is a benign to low-grade malignant neoplasm most commonly occurring in the viscera and soft tissues of children and young adults. Involvement of the breast is very rare. This report presents the first case of IMT of the nipple and highlights the histologic features and differential diagnosis at this unusual anatomical site. The patient was a 31-years-old pregnant woman with a palpable mass at the upper half of the left nipple. The lesion appeared after breastfeeding of her first child and increased in size during her second pregnancy. A conservative, incomplete surgical excision was performed in the 24th week of the second pregnancy. The residual tumor subsequently underwent spontaneous regression. There was no evidence of disease 5years after surgery. FISH and immunohistochemical analyses revealed rearrangement and overexpression of the ALK gene, a typical feature of both pulmonary and extrapulmonary IMT.
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| 39. |
- Kovács, Anikó, 1961, et al.
(author)
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Bowen's disease: statistical study of a 10 year period.
- 1996
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In: The Journal of dermatology. - 0385-2407. ; 23:4, s. 267-74
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Journal article (peer-reviewed)abstract
- According to histological records, a total of 74 patients were diagnosed with Bowen's disease (B.d.) between 1 January 1984 and 31 December 1993 at the Department of Dermatology of Kitasato University. There was slight female predominance (36 male, 38 female), and 73% of the patients were older than 60 years; the mean age was 66.8 years. Fifteen patients had multiple (two-five) lesions. In 13 patients, other benign skin lesions were also found. Arsenic exposure as etiologic factor could have been present in 2 cases. Only 3 patients had other associated malignant tumors, which does not confirm the paraneoplastic nature of B.d. One-fifth of the lesions were on sun-exposed areas (head, neck and hands). Although we excluded invasive carcinomas from our statistical study, we mention the 8 invasive carcinomas developing from B.d. in that period. Histopathological classification of B.d. is uncommon. Classifying our cases by Darier's histopathological classification, 63.3% of them belonged to the lenticular type. The malignant potential of different histopathological types of B.d. needs further investigation.
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| 40. |
- Kovács, Anikó, 1961, et al.
(author)
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Effect of Radiotherapy After Breast-Conserving Surgery Depending on the Presence of Tumor-Infiltrating Lymphocytes : A Long-Term Follow-Up of the SweBCG91RT Randomized Trial
- 2019
-
In: Journal of Clinical Oncology. - 0732-183X. ; 37:14, s. 1179-87
-
Journal article (peer-reviewed)abstract
- PURPOSE: The effects of radiotherapy (RT) on the basis of the presence of stromal tumor infiltrating lymphocytes (TILs) have not been studied. The purpose of this study was to analyze the association of TILs with the effect of postoperative RT on ipsilateral breast tumor recurrence (IBTR) in a large randomized trial. METHODS: In the SweBCT91RT (Swedish Breast Cancer Group 91 Radiotherapy) trial, 1,178 patients with breast cancer stage I and II were randomly assigned to breast-conserving surgery plus postoperative RT or breast-conserving surgery only and followed for a median of 15.2 years. Tumor blocks were retrieved from 1,003 patients. Stromal TILs were assessed on whole-section hematoxylin-eosin-stained slides using a dichotomized cutoff of 10%. Subtypes were scored using immunohistochemistry on tissue microarray. In total, 936 patients were evaluated. RESULTS: Altogether, 670 (71%) of patients had TILs less than 10%. In a multivariable regression analysis with IBTR as dependent variable and RT, TILs, subtype, age, and grade as independent variables, RT (hazard ratio [HR], 0.42; 95% CI, 0.29 to 0.61; P < .001), high TILs (HR, 0.61; 95% CI, 0.39 to 0.96, P = .033) grade (3 v 1; HR, 2.17; 95% CI, 1.08 to 4.34; P = .029), and age (≥ 50 v < 50 years; HR, 0.55; 95% CI, 0.38 to 0.80; P = .002) were predictive of IBTR. RT was significantly beneficial in the low TILs group (HR, 0.37; 95% CI, 0.24 to 0.58; P < .001) but not in the high TILs group (HR, 0.58; 95% CI, 0.28 to 1.19; P = .138). The test for interaction between RT and TILs was not statistically significant (P = .317). CONCLUSION: This study shows that high values of TILs in the primary tumor independently seem to reduce the risk for an IBTR. Our findings further suggest that patients with breast cancer with low TILs may derive a larger benefit from RT regarding the risk of IBTR.
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| 41. |
- Kovács, Anikó, 1961, et al.
(author)
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Immunohistochemical examination of P-cadherin in bullous and acantholytic skin diseases.
- 2004
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In: Acta dermato-venereologica. - : Medical Journals Sweden AB. - 0001-5555. ; 84:2, s. 116-9
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Journal article (peer-reviewed)abstract
- Autoimmune blistering diseases (pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, dermatitis herpetiformis) and certain genodermatoses with acantholysis (Darier-disease, Hailey-Hailey disease) have different aetiological factors, but all result in bulla formation and/or in acantholysis. Cadherins are Ca++-dependent cell-cell adhesion molecules which play an important role in the cellular connection between normal cells. P-cadherin is involved in the selective adhesion of epidermal cells, and is expressed only on the surfaces of the two basal layers. We examined the expression of P-cadherin in some autoimmune bullous skin diseases and Darier's disease using immunohistochemistry and found P-cadherin to be strongly upregulated. We believe the upregulation is compensatory to the primary pathophysiological events in the various bullous dermatoses.
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| 42. |
- Kovács, Anikó, 1961, et al.
(author)
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[Immunohistochemical study of P-cadherin in breast cancer]. : P-cadherin immunhisztokémiai vizsgálata emlórákokban.
- 2002
-
In: Orvosi hetilap. - 0030-6002. ; 143:8, s. 405-9
-
Journal article (peer-reviewed)abstract
- Cell adhesion molecules play a significant role in the cellular connection of normal cells. The cadherins are believed to act as tumour suppressors, and their altered expression and function have been associated with tumour development.The authors examined the expression of a Ca++ dependent intercellular adhesion molecule, P-cadherin using an immunohistochemical method in 69 surgically resected breast carcinomas.P-cadherin was detected in 30 cases (43.5%, cytoplasmic and/or membrane staining). The expression of P-cadherin was independent of tumour size and lymph node status, but correlated with a high tumour grade (grade III). In contrast, expression of E-cadherin correlated with lower tumour grade (grade I-II). P-cadherin expression was not detected in invasive lobular carcinomas.In general, P-cadherin was expressed at a lower frequency compared to E-cadherin, alpha-, and beta-catenin. These results suggest that an inverse relationship may exist between E- and P-cadherin in relation to grade, and that the expression of P-cadherin may be a marker of aggressiveness.
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| 43. |
- Kovács, Anikó, 1961, et al.
(author)
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P-cadherin as a marker in the differential diagnosis of breast lesions.
- 2003
-
In: Journal of clinical pathology. - : BMJ. - 0021-9746. ; 56:2, s. 139-41
-
Journal article (peer-reviewed)abstract
- To assess the value of the calcium dependent cell adhesion molecule P-cadherin as a myoepithelial marker in the differential diagnosis of benign and malignant breast lesions.Immunohistochemical analysis of normal breast, sclerotic breast lesions, tubular carcinomas, and ductal carcinoma in situ using a P-cadherin specific antibody and comparison with smooth muscle actin.All myoepithelial cells in normal breast ducts, ductules, and lobules and sclerotic lesions showed strong staining for P-cadherin. There was no staining of tubular carcinomas; myoepithelial cells were demonstrated around in situ carcinomas. Weaker reactivity was seen in a proportion of cells in some hyperplasias and in situ carcinomas. This weak reactivity in these tissues was not seen for smooth muscle actin but in radial scars, tubular carcinomas, and ductal carcinoma in situ staining of stromal cells caused difficulties in the identification of myoepithelial cells.P-cadherin is a useful marker in the differential diagnosis of breast lesions.
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| 44. |
- Kovács, Anikó, 1961, et al.
(author)
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Spousal Cancer: A Systematic Review and Case Report of a Metachronous Presentation of Breast Cancer in a Genetically Unrelated Couple
- 2017
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In: Clinics in Oncology. - 2474-1663. ; 2
-
Research review (peer-reviewed)abstract
- We present a systematic review of the literature about spousal cancer, concerning the possible cancer aetiology of synchronous and metachronous, concordant and discordant cancer types in married couples. Synchronous and metachronous breast cancer in spouses are extremely rare. We present here a married couple whom were diagnosed with metachronous breast cancer, with a 10year delay in onset in the husband. This case of spousal breast cancer may represent a coincidental phenomenon, as breast cancer is quite uncommon in men. It has been postulated that exposure to viral, nutritional and environmental / contamination factors for extended periods of time might facilitate cancer development in the same organ in spouses. However, current cancer incidence rates among cohabitants are relatively low.
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| 45. |
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| 46. |
- Landén, Amalia H, et al.
(author)
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Evaluation of tumor-infiltrating lymphocytes and mammographic density as predictors of response to neoadjuvant systemic therapy in breast cancer.
- 2023
-
In: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 62:12, s. 1862-1872
-
Journal article (peer-reviewed)abstract
- Response rates vary among breast cancer patients treated with neoadjuvant systemic therapy (NAST). Thus, there is a need for reliable treatment predictors. Evidence suggests tumor-infiltrating lymphocytes (TILs) predict NAST response. Still, TILs are seldom used clinically as a treatment determinant. Mammographic density (MD) is another potential marker for NAST benefit and its relationship with TILs is unknown. Our aims were to investigate TILs and MD as predictors of NAST response and to study the unexplored relationship between TILs and MD.We studied 315 invasive breast carcinomas treated with NAST between 2013 and 2020. Clinicopathological data were retrieved from medical records. The endpoint was defined as pathological complete response (pCR) in the breast. TILs were evaluated in pre-treatment core biopsies and categorized as high (≥10%) or low (<10%). MD was scored (a-d) according to the breast imaging reporting and data system (BI-RADS) fifth edition. Binary logistic regression and Spearman's test of correlation were performed using SPSS.Out of 315 carcinomas, 136 achieved pCR. 94 carcinomas had high TILs and 215 had low TILs. Six carcinomas had no available TIL data. The number of carcinomas in each BI-RADS category were 37, 122, 112, and 44 for a, b, c, and d, respectively. High TILs were independently associated with pCR (OR: 2.95; 95% CI: 1.59-5.46) compared to low TILs. In the univariable analysis, MD (BI-RADS d vs. a) showed a tendency of higher likelihood for pCR (OR: 2.43; 95% CI: 0.99-5.98). However, the association was non-significant, which is consistent with the result of the multivariable analysis (OR: 2.51; 95% CI: 0.78-8.04). We found no correlation between TILs and MD (0.02; p=.80).TILs significantly predicted NAST response. We could not define MD as a significant predictor of NAST response. These findings should be further replicated.
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| 47. |
- Larsson, Peter, et al.
(author)
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Optimization of cell viability assays to improve replicability and reproducibility of cancer drug sensitivity screens.
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- Cancer drug development has been riddled with high attrition rates, in part, due to poor reproducibility of preclinical models for drug discovery. Poor experimental design and lack of scientific transparency may cause experimental biases that in turn affect data quality, robustness and reproducibility. Here, we pinpoint sources of experimental variability in conventional 2D cell-based cancer drug screens to determine the effect of confounders on cell viability for MCF7 and HCC38 breast cancer cell lines treated with platinum agents (cisplatin and carboplatin) and a proteasome inhibitor (bortezomib). Variance component analysis demonstrated that variations in cell viability were primarily associated with the choice of pharmaceutical drug and cell line, and less likely to be due to the type of growth medium or assay incubation time. Furthermore, careful consideration should be given to different methods of storing diluted pharmaceutical drugs and use of DMSO controls due to the potential risk of evaporation and the subsequent effect on dose-response curves. Optimization of experimental parameters not only improved data quality substantially but also resulted in reproducible results for bortezomib- and cisplatin-treated HCC38, MCF7, MCF-10A, and MDA-MB-436 cells. Taken together, these findings indicate that replicability (the same analyst re-performs the same experiment multiple times) and reproducibility (different analysts perform the same experiment using different experimental conditions) for cell-based drug screens can be improved by identifying potential confounders and subsequent optimization of experimental parameters for each cell line.
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| 48. |
- Larsson, Peter, et al.
(author)
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Pan-cancer analysis of genomic and transcriptomic data reveals the prognostic relevance of human proteasome genes in different cancer types.
- 2022
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In: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 22
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Journal article (peer-reviewed)abstract
- The human proteasome gene family (PSM) consists of 49 genes that play a crucial role in cancer proteostasis. However, little is known about the effect of PSM gene expression and genetic alterations on clinical outcome in different cancer forms.Here, we performed a comprehensive pan-cancer analysis of genetic alterations in PSM genes and the subsequent prognostic value of PSM expression using data from The Cancer Genome Atlas (TCGA) containing over 10,000 samples representing up to 33 different cancer types. External validation was performed using a breast cancer cohort and KM plotter with four cancer types.The PSM genetic alteration frequency was high in certain cancer types (e.g. 67%; esophageal adenocarcinoma), with DNA amplification being most common. Compared with normal tissue, most PSM genes were predominantly overexpressed in cancer. Survival analysis also established a relationship with PSM gene expression and adverse clinical outcome, where PSMA1 and PSMD11 expression were linked to more unfavorable prognosis in≥30% of cancer types for both overall survival (OS) and relapse-free interval (PFI). Interestingly, PSMB5 gene expression was associated with OS (36%) and PFI (27%), and OS for PSMD2 (42%), especially when overexpressed.These findings indicate that several PSM genes may potentially be prognostic biomarkers and novel therapeutic targets for different cancer forms.
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| 49. |
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| 50. |
- Larsson Wexell, Cecilia, 1965, et al.
(author)
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A Case Report on Gardner Syndrome With Dental Implant Treatment and a Long-Term Follow-Up.
- 2019
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In: Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. - : Elsevier BV. - 1531-5053. ; 77:8, s. 1617-1627
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Journal article (peer-reviewed)abstract
- A case of Gardner syndrome (GS) in a 37-year-old woman is presented in which rehabilitation with dental implant treatment was followed for 7years. The course of diagnostics and treatment is followed through an overview of 45 tissue biopsy and cytology samples during a period of 30years. The patient was diagnosed with GS after a routine review of an oral panoramic radiograph presenting with multiple osteomas and multiple unerupted supernumerary teeth. Biopsy results and surgical procedures with histopathologic diagnoses from 1986 to 2016 are presented. Histologic analysis of the sampled jawbone showed a picture similar to an osteoid osteoma. The installed implant was functionally stable, with no clinical or radiographic events observed at yearly visits, for 7years. In 1991, benign tumors appeared; in 2014, multiple adenomas were found in the small intestine and rectum. This case report shows the potential for dental implant treatment in a patient with GS.
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