| 1. |
- Biermann, Jana, et al.
(författare)
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Clonal relatedness in tumour pairs of breast cancer patients.
- 2018
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Ingår i: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-542X. ; 20:1
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Biermann, Jana, et al.
(författare)
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Tumour clonality in paired invasive breast carcinomas
- 2019
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Ingår i: Cancer Research. - 0008-5472.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)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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| 3. |
- Axelsson, Lars, et al.
(författare)
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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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Ingår i: Journal of Otolaryngology-Head & Neck Surgery. - : Springer Science and Business Media LLC. - 1916-0216. ; 46
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Tidskriftsartikel (refereegranskat)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. |
- Biermann, Jana, et al.
(författare)
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Radiation-induced genomic instability in breast carcinomas of the Swedish haemangioma cohort.
- 2019
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Ingår i: Genes, chromosomes & cancer. - : Wiley. - 1098-2264 .- 1045-2257. ; 58:9, s. 627-35
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Tidskriftsartikel (refereegranskat)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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| 5. |
- De Lara, Shahin, et al.
(författare)
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GATA3 as a putative marker of breast cancer metastasis-A retrospective immunohistochemical study.
- 2018
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Ingår i: The breast journal. - : Hindawi Limited. - 1524-4741 .- 1075-122X. ; 24:2, s. 184-188
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Tidskriftsartikel (refereegranskat)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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| 6. |
- De Lara, Shahin, 1966, et al.
(författare)
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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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Ingår i: Bmc Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 19
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Tidskriftsartikel (refereegranskat)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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| 7. |
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| 8. |
- Engqvist, Hanna, 1985, et al.
(författare)
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Immunohistochemical validation of COL3A1, GPR158 and PITHD1 as prognostic biomarkers in early-stage ovarian carcinomasn
- 2019
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 19:1
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Tidskriftsartikel (refereegranskat)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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| 9. |
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| 10. |
- Kimbung, Siker, et al.
(författare)
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Contrasting breast cancer molecular subtypes across serial tumor progression stages: biological and prognostic implications.
- 2015
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:32, s. 33306-18
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Tidskriftsartikel (refereegranskat)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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