| 1. |
- Arildsen, Nicolai Skovbjerg, et al.
(författare)
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Involvement of chromatin remodeling genes and the Rho GTPases RhoB and CDC42 in ovarian clear cell carcinoma
- 2017
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 7:MAY, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Ovarian clear cell carcinomas (OCCCs) constitute a rare ovarian cancer subtype with distinct clinical features, but may nonetheless be difficult to distinguish morphologically from other subtypes. There is limited knowledge of genetic events driving OCCC tumorigenesis beyond ARID1A, which is reportedly mutated in 30-50% of OCCCs. We aimed to further characterize OCCCs by combined global transcriptional profiling and targeted deep sequencing of a panel of well-established cancer genes. Increased knowledge of OCCC-specific genetic aberrations may help in guiding development of targeted treatments and ultimately improve patient outcome. Methods: Gene expression profiling of formalin-fixed, paraffin-embedded (FFPE) tissue from a cohort of the major ovarian cancer subtypes (cohort 1; n = 67) was performed using whole-genome cDNA-mediated Annealing, Selection, extension and Ligation (WG-DASL) bead arrays, followed by pathway, gene module score, and gene ontology analyses, respectively. A second FFPE cohort of 10 primary OCCCs was analyzed by targeted DNA sequencing of a panel of 60 cancer-related genes (cohort 2). Non-synonymous and non-sense variants affecting single-nucleotide variations and insertions or deletions were further analyzed. A tissue microarray of 43 OCCCs (cohort 3) was used for validation by immunohistochemistry and chromogenic in situ hybridization. Results: Gene expression analyses revealed a distinct OCCC profile compared to other histological subtypes, with, e.g., ERBB2, TFAP2A, and genes related to cytoskeletal actin regulation being overexpressed in OCCC. ERBB2 was, however, not overexpressed on the protein level and ERBB2 amplification was rare in the validation cohort. Targeted deep sequencing revealed non-synonymous variants or insertions/deletions in 11/60 cancer-related genes. Genes involved in chromatin remodeling, including ARID1A, SPOP, and KMT2D were frequently mutated across OCCC tumors. Conclusion: OCCCs appear genetically heterogeneous, but harbor frequent alterations in chromatin remodeling genes. Overexpression of TFAP2A and ERBB2 was observed on the mRNA level in relation to other ovarian cancer subtypes. However, overexpression of ERBB2 was not reflected by HER2 amplification or protein overexpression in the OCCC validation cohort. In addition, Rho GTPase-dependent actin organization may also play a role in OCCC pathogenesis and warrants further investigation. The distinct biological features of OCCC discovered here may provide a basis for novel targeted treatment strategies.
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| 2. |
- Bååth, Maria, et al.
(författare)
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SOX2 is a promising predictor of relapse and death in advanced stage high-grade serous ovarian cancer patients with residual disease after debulking surgery
- 2020
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Ingår i: Molecular and Cellular Oncology. - : Informa UK Limited. - 2372-3556. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- The transcription factor SOX2 is a well-established and important stem cell marker. Its role in cancer biology remains unclear, but it has been proposed to also be a marker of cancer stem cells. We investigated the role of SOX2 protein expression in women with high-grade serous ovarian cancer (HGSOC) to determine its potential prognostic and treatment predictive value. We constructed a tissue microarray of 130 advanced stage HGSOC tumors with an average of 6 cores each, stained for SOX2 protein expression and evaluated survival outcomes. We also treated two HGSOC cell lines with carboplatin and paclitaxel and measured SOX2 expression by RT-PCR and immunoblotting at different doses and time-points. Among patients with non-radical debulking surgery overall and progression-free survival were shorter for patients with SOX2 positive tumors (mean 26 vs. 39 months, log-rank test: p = .0076, and mean 14 vs. 19 months, p = .055, respectively). Knockdown of SOX2 in cell lines did not affect growth inhibition following chemotherapy treatment. Our results show that SOX2 has a strong prognostic potential among HGSOC patients with residual tumor tissue after debulking surgery and suggest that SOX2 expressing cells remaining after non-radical debulking surgery may constitute a subpopulation of cancer stem cells with greater tumor-initiating potential.
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| 3. |
- Epstein, Elisabeth, et al.
(författare)
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Early-stage cervical cancer: Tumor delineation by magnetic resonance imaging and ultrasound - A European multicenter trial
- 2013
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 128:3, s. 449-453
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To compare the diagnostic accuracy of ultrasound (US) and magnetic resonance imaging (MRI) in the preoperative assessment of early-stage cervical cancer using pathologic findings as the reference standard. Patients and methods. Prospective multi-center trial enrolling 209 consecutive women with early-stage cervical cancer (FIGO IA2-IIA) scheduled for surgery. The following parameters were assessed on US and MRI and compared to pathology: remaining tumor, size, tumor stromal invasion <2/3 (superficial) or >= 2/3 (deep), and parametrial invasion. Results. Complete data were available for 182 patients. The agreement between US and pathology was excellent for detecting tumors, correctly classifying bulky tumors (>4 cm), and detecting deep stromal invasion (kappa values 0.84, 0.82, and 0.81 respectively); and good for classifying small tumors (<2 cm) and detecting parametrial invasion (kappa values 0.78 and 0.75, respectively). The agreement between MRI and histology was good for classifying tumors as <2 cm, or >4 cm, and detecting deep stromal invasion (kappa values 0.71, 0.76, and 0.77, respectively). It was Moderately accurate in tumor detection, and in assessing parametrial invasion (kappa values 0.52 and 0.45, respectively). The agreement between histology and US was significantly better in assessing residual tumor (p<0.001) and parametrial invasion (p<0.001) than the results obtained by MRI. Imaging methods were not significantly influenced by previous cone biopsy. Conclusion. US and MRI are highly accurate for the preoperative assessment of women with early-stage cervical cancer, although US may be more accurate in detecting residual tumors and assessing parametrial invasion. (C) 2012 Elsevier Inc. All rights reserved.
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| 4. |
- Harbst, Katja, et al.
(författare)
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Molecular profiling reveals low- and high-grade forms of primary melanoma.
- 2012
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Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1557-3265. ; 18:15, s. 4026-4036
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Tidskriftsartikel (refereegranskat)abstract
- For primary melanomas, tumor thickness, mitotic rate, and ulceration are well-laid cornerstones of prognostication. However, a molecular exposition of melanoma aggressiveness is critically missing. We recently uncovered a four-class structure in metastatic melanoma, which predicts outcome and informs biology. This raises the possibility that a molecular structure exists even in the early stages of melanoma and that molecular determinants could underlie histophenotype and eventual patient outcome.We subjected 223 archival primary melanomas to a horizontally integrated analysis of RNA expression, oncogenic mutations at 238 lesions, histomorphometry, and survival data.Our previously described four-class structure that was elucidated in metastatic lesions was evident within the expression space of primary melanomas. Because these subclasses converged into two larger prognostic and phenotypic groups, we used the metastatic lesions to develop a binary subtype-based signature capable of distinguishing between "high" and "low" grade forms of the disease. The two-grade signature was subsequently applied to the primary melanomas. Compared with low-grade tumors, high-grade primary melanomas were significantly associated with increased tumor thickness, mitotic rate, ulceration (all P < 0.01), and poorer relapse-free (HR = 4.94; 95% CI, 2.84-8.59), and overall (HR = 3.66; 95% CI, 2.40-5.58) survival. High-grade melanomas exhibited elevated levels of proliferation and BRCA1/DNA damage signaling genes, whereas low-grade lesions harbored higher expression of immune genes. Importantly, the molecular-grade signature was validated in two external gene expression data sets.We provide evidence for a molecular organization within melanomas, which is preserved across all stages of disease.
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| 5. |
- Koebel, Martin, et al.
(författare)
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Ovarian carcinoma histotype determination is highly reproducible, and is improved through the use of immunohistochemistry
- 2014
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 94, s. 290A-290A
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Tidskriftsartikel (refereegranskat)abstract
- AimsTo assess the variation in ovarian carcinoma type diagnosis among gynaecological pathologists from Nordic countries, and whether a rationally designed panel of immunohistochemical markers could improve diagnostic reproducibility. Methods and resultsEight pathologists from four countries (Sweden, Denmark, Norway, and Finland) received an educational lecture on the diagnosis of ovarian carcinoma type. All tumour-containing slides from 54 ovarian carcinoma cases were independently reviewed by the participants, who: (i) determined type purely on the basis of histology; (ii) indicated whether they would apply immunohistochemistry in their routine practice; and (iii) determined type after reviewing the staining results. The results for six markers (WT1, p53, p16, HNF-1, ARID1A, and progesterone receptor) were determined for all 54 cases, by staining of a tissue microarray. The median concordance with central review diagnosis was 86%, and significantly improved to 90% with the incorporation of immunostaining results (P=0.0002). The median interobserver agreement was 78%, and significantly improved to 85% with the incorporation of immunostaining results (P=0.0002). ConclusionsUse of the immunostaining results significantly improved both diagnostic accuracy and interobserver agreement. These results indicate that ovarian carcinoma type can be reliably diagnosed by pathologists from different countries, and also demonstrate that immunohistochemistry has an important role in improving diagnostic accuracy and agreement between pathologists.
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| 6. |
- Martín De La Fuente, Laura, et al.
(författare)
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Claudin-4 Expression is Associated with Survival in Ovarian Cancer but Not with Chemotherapy Response
- 2018
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Ingår i: International Journal of Gynecological Pathology. - 0277-1691. ; 37:2, s. 101-109
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Tidskriftsartikel (refereegranskat)abstract
- The tight junction protein claudin-4 has been reported to be overexpressed in advanced ovarian cancer. We investigated the prognostic significance of claudin-4 overexpression and whether claudin-4 expression could predict platinum response in primary ovarian carcinoma (OC). Claudin-4 expression was evaluated by immunohistochemistry in a tissue microarray of 140 OCs. Multivariable Cox-regression models were used to assess the effect of claudin-4 overexpression on progression-free survival and overall survival (OS). Kaplan-Meier survival analyses and the logrank test were performed comparing claudin-4 high and low groups. The association between claudin-4 expression and platinum resistance was assessed using risk ratios and the Pearson χ 2 test. A dataset of >1500 epithelial ovarian cancers was used to study the association between CLDN4 mRNA and survival. Of 140 evaluable cases, 71 (51%) displayed high claudin-4 expression. Claudin-4 overexpression predicted shorter 5-yr progression-free survival and OS in univariable analyses [hazard ratio (HR)=1.6 (1.1-2.5), P=0.020 and HR=1.6 (1.0-2.4), P=0.041, respectively]. Hazard of relapse was similar [HR=1.5 (1.0-2.4)] after adjustment for age, stage, type, and BRCA1/2 status in a multivariable analysis, but the evidence was slightly weaker (P=0.076). Validation in an external cohort confirmed the association between high expression of CLDN4 and poor 10-yr OS [HR=1.3 (1.1-1.5), P<0.001]. However, no confident association between claudin-4 and platinum sensitivity was found in our cohort [risk ratio=1.2 (0.7-2.0), P=0.3]. These findings suggest that high expression of claudin-4 may have a prognostic value in OC. The role of claudin-4 in the development of platinum resistance remains unclear.
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| 7. |
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| 8. |
- Arildsen, Nicolai Skovbjerg, et al.
(författare)
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Detecting TP53 mutations in diagnostic and archival liquid-based Pap samples from ovarian cancer patients using an ultra-sensitive ddPCR method
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- High-grade serous ovarian cancer (HGSOC) is the most common subtype of epithelial ovarian cancer and early detection is challenging. TP53 mutations are a hallmark of HGSOC and detection of these mutations in liquid-based Pap samples could provide a method for early diagnosis. Here we evaluate the use of IBSAFE, an ultra-sensitive droplet digital PCR (ddPCR) method, for detecting TP53 mutations in liquid-based Pap samples collected from fifteen women at the time of diagnosis (diagnostic samples) and/or up to seven years prior to diagnosis (archival samples). We analysed tumours for somatic TP53 mutations with next generation sequencing and were able to detect the corresponding mutations in diagnostic samples from six of eight women, while one patient harboured a germline mutation. We further detected a mutation in an archival sample obtained 20 months prior to the ovarian cancer diagnosis. The custom designed IBSAFE assays detected minor allele frequencies (MAFs) with very high assay sensitivity (MAF = 0.0068%) and were successful despite low DNA abundance (0.17-206.14 ng, median: 17.27 ng). These results provide support for further evaluation of archival liquid-based Pap samples for diagnostic purposes and demonstrate that ultra-sensitive ddPCR should be evaluated for ovarian cancer screening in high-risk groups or in the recurrent setting.
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| 9. |
- Asp, Mihaela, et al.
(författare)
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Ovarian tumor frozen section, a multidisciplinary affair
- 2022
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Ingår i: Acta Oncologica. - 1651-226X. ; 61:7, s. 785-792
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundOvarian Cancer (OC) constitute the eighth most common cancers among women worldwide. Surgery remains the cornerstone in the management of OC. Intraoperative frozen section (FS) diagnosis is widely used to decide the surgery course. We aimed to assess the reliability of intraoperative FS diagnosis for treatment planning of patients with suspected OC from a multidisciplinary perspective. The clinical consequences of reclassification and the multidisciplinary management of the therapy plan, is the secondary aim of this study. To our knowledge, this information is sparely investigated.MethodsA single-center, retrospective population-based study of patients who underwent surgery for suspected OC between 2018 and 2020. Histopathological outcomes were classified as benign, borderline, or malignant. The FS diagnosis was the diagnostic test, and the final histopathology report was the gold standard. Diagnostic capability for treatment planning was assessed, and modifications made possible by overall clinical knowledge were discussed.ResultsA total of 358 patients were identified, of whom 187 were included in the FS group. Overall accuracy was 89.8%, and 19 patients were reclassified; the malignancy grade of 15 tumors was underestimated. Prevalence, sensitivity, specificity, positive predictive value, and negative predictive value for invasive malignancies on FS were 54.0% (CI 46.6–61.3%), 88.1% (CI 80.2–93.7%), 98.8% (CI 93.7–99.9%), 98.9% (CI 92.7–99.8%), and 87.6% (CI 80.6–92.4%), respectively. Tumors incorrectly graded by FS tended to be of borderline-related.ConclusionsThe reliability of the FS methodology was an accurate test to help perform appropriate surgery and plan swift oncological treatment. FS is a reliable method to diagnose invasive malignancies and benign pathology. The communication between the pathologist, surgeon, and medical oncologist is highly important for both intraoperative decision-making and postoperative patient care.
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| 10. |
- Asp, Mihaela, et al.
(författare)
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Tru-Cut Biopsy in Gynecological Cancer: Adequacy, Accuracy, Safety and Clinical Applicability
- 2023
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Ingår i: Journal of Multidisciplinary Healthcare. - 1178-2390. ; 16, s. 1367-1377
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Tru-cut biopsy is a minimally invasive technique used to obtain tissue samples for the diagnosis of tumors, especially in patients where primary surgery is not indicated. The aim of this study was to assess the adequacy, accuracy and safety of the tru-cut biopsy for diagnosis in gynecological cancer.Methods: A retrospective population-based review of 328 biopsies was conducted. The indications for tru-cut biopsies were diagnosis of primary tumors, metastases of gynecological and non-gynecological tumors, and suspected recurrences. A tissue sample was considered adequate when the quality/quality was sufficient to identify the subtype/origin of the tumor. Potential factors affecting adequacy were analyzed using logistic regressions analyses. Accuracy was defined as agreement between the diagnosis of the tru-cut biopsy and the postoperative histology. The therapy plan was registered, and the clinical applicability of the tru-cut biopsy was investigated. Complications within 30 days after the biopsy procedure were registered.Results: In total, 300 biopsies were identified as tru-cut biopsies. The overall adequacy was 86.3%, varying between 80.8% and 93.5%, respectively, when performed by a gynecological oncologist or a gynecologist with a subspecialty in ultrasound diagnosis. Sampling of a pelvic mass had a lower adequacy (81.6%) compared with sampling of the omentum (93.9%) or carcinomatosis (91.5%). The accuracy was 97.5%, and the complication rate was 1.3%.Conclusion: The tru-cut biopsy is a safe and reliable diagnostic method with a high accuracy and a good adequacy, depending on the site of the tissue sample, indications for the biopsy and the experience of the operator.
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| 11. |
- Bartuma, Katarina, et al.
(författare)
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Ovarian cancer at young age: the contribution of mismatch-repair defects in a population-based series of epithelial ovarian cancer before age 40.
- 2007
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Ingår i: International Journal of Gynecological Cancer. - : BMJ. - 1048-891X .- 1525-1438. ; 17, s. 789-793
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Tidskriftsartikel (refereegranskat)abstract
- At least one of ten patients with ovarian cancer is estimated to develop their tumor because of heredity with the breast and ovarian cancer syndrome due to mutations in the BRCA1 and BRCA2 genes and hereditary nonpolyposis colorectal cancer (HNPCC) being the major genetic causes. Cancer at young age is a hallmark of heredity, and ovarian cancers associated with HNPCC have been demonstrated to develop at a particularly early age. We used the Swedish Cancer Registry to identify a population-based series of 98 invasive epithelial ovarian cancers that developed before 40 years. Mucinous and endometrioid cancers were overrepresented and were diagnosed in 27% and 16% of the tumors, respectively. Immunostaining using antibodies against MLH1, PMS2, MSH2, and MSH6 was used to assess the mismatch-repair status and revealed loss of expression of MLH1/PMS2 in two cases, loss of MSH2/MSH6 in one case, and loss of MSH6 only in three tumors. A microsatellite instability–high phenotype was verified in five of six tumors. Based on the identified mutations and family history of cancer, several of these individuals are likely to be affected by HNPCC. We conclude that although the causes of the vast majority of epithelial ovarian cancer at young age are unknown, HNPCC should be considered because of the high risk of metachronous colorectal cancer in the individual and the possibility of preventing additional cancers in the family through control programs.
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| 12. |
- Binzer-Panchal, Amrei, et al.
(författare)
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Integrated Molecular Analysis of Undifferentiated Uterine Sarcomas Reveals Clinically Relevant Molecular Subtypes
- 2019
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Ingår i: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 25:7, s. 2155-2165
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Undifferentiated uterine sarcomas (UUS) are rare, extremely deadly, sarcomas with no effective treatment. The goal of this study was to identify novel intrinsic molecular UUS subtypes using integrated clinical, histopathologic, and molecular evaluation of a large, fully annotated, patient cohort.Experimental Design: Fifty cases of UUS with full clinicopathologic annotation were analyzed for gene expression (n = 50), copy-number variation (CNV, n = 40), cell morphometry (n = 39), and protein expression (n = 22). Gene ontology and network enrichment analysis were used to relate over-and underexpressed genes to pathways and further to clinicopathologic and phenotypic findings.Results: Gene expression identified four distinct groups of tumors, which varied in their clinicopathologic parameters. Gene ontology analysis revealed differential activation of pathways related to genital tract development, extracellular matrix (ECM), muscle function, and proliferation. A multivariable, adjusted Cox proportional hazard model demonstrated that RNA group, mitotic index, and hormone receptor expression influence patient overall survival (OS). CNV arrays revealed characteristic chromosomal changes for each group. Morphometry demonstrated that the ECM group, the most aggressive, exhibited a decreased cell density and increased nuclear area. A cell density cutoff of 4,300 tumor cells per mm(2) could separate ECM tumors from the remaining cases with a sensitivity of 83% and a specificity of 94%. IHC staining of MMP-14, Collagens 1 and 6, and Fibronectin proteins revealed differential expression of these ECM-related proteins, identifying potential new biomarkers for this aggressive sarcoma subgroup. Conclusions: Molecular evaluation of UUS provides novel insights into the biology, prognosis, phenotype, and possible treatment of these tumors.
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| 13. |
- Borgfeldt, Christer, et al.
(författare)
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Dedifferentiation of serous ovarian cancer from cystic to solid tumors is associated with increased expression of mRNA for urokinase plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1)
- 2001
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 92:4, s. 497-502
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Tidskriftsartikel (refereegranskat)abstract
- The plasminogen activating system is involved in tumor growth and metastasis by degradation of extracellular matrix, and modulation of cell adhesion and migration. Benign and well-differentiated malignant ovarian tumors present as cystic lesions with preserved glandular morphology, whereas poorly differentiated tumors and metastases are solid with characteristic absence of glandular morphology. We analyzed the mRNAs for urokinase plasminogen activator (uPA), its receptor (uPAR), and inhibitor (PAI-1) in serous ovarian tumors by in situ hybridization and by densitometric scanning of Northern blots prepared from tissue extracts. The mRNA expressing cells in the in situ hybridization sections were evaluated and counted by two different observers. The number of mRNA expressing cells for uPA, uPAR and PAI-1 were all significantly increased in solid as compared with cystic malignant tumors. The increased expression of all three mRNA species was mainly located in the stroma of poorly differentiated tumors and metastases. Apart from being expressed in the stroma of these tumors, uPAR mRNA was also expressed by tumor cells located along the stromal/epithelial boarder. In addition, the tumor tissue content of uPA, uPAR and PAI-1 mRNAs as measured by Northern blots were higher in the solid as compared with the cystic tumors. Increased expression of uPA, uPAR and PAI-1 genes in the solid tumors suggest a correlation with a more aggressive phenotype.
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| 14. |
- Borgfeldt, Christer, et al.
(författare)
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Fertility-sparing surgery and outcome in fertile women with ovarian borderline tumors and epithelial invasive ovarian cancer.
- 2007
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Ingår i: European Journal of Obstetrics, Gynecology, and Reproductive Biology. - : Elsevier BV. - 0301-2115. ; 134:1, s. 110-114
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim was to evaluate the outcome of fertility-sparing treatment in ovarian borderline tumors and early invasive ovarian cancer. Materials and methods: All women diagnosed with an ovarian borderline tumor or early invasive ovarian cancer who were treated with fertility-sparing surgery at the University Hospital in Lund between 1988 and 2002 were identified and included in the study (n = 23). Results: During the follow-up period of a median 92 months, range 11-185 months, no relapse was found in the patients with Stage 1a tumors, including both borderline tumors (n = 12) and invasive well-differentiated (n = 9) and moderately differentiated (n = 1) ovarian cancers. One patient with poorly differentiated ovarian cancer Stage 1c was 13 weeks' pregnant at the time of the primary operation. Although, unilateral oophorectomy was performed she insisted on continuing the pregnancy. At 37 weeks she had a cesarean section and the ovarian cancer was disseminated. Chemotherapy was given but she died less than a year later. None of the other patients received chemotherapy. In total, 30 children were born to 15 patients. Prophylactic removal of the remaining ovary hysterectomy was accepted in only in six of the women after fulfilling their desire to have more children. Conclusions: Young women with Stage 1a epithelial ovarian cancer and borderline tumors do not have to give up their fertility in order to receive successful and safe treatment of their disease. However, several of these patients do not accept the recommendation of prophylactic oophorectomy of the contralateral ovary and hysterectomy after completion of childbearing. (C) 2006 Elsevier Ireland Ltd. All rights reserved.
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| 15. |
- Bååth, Maria, et al.
(författare)
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MET Expression and Cancer Stem Cell Networks Impact Outcome in High-Grade Serous Ovarian Cancer
- 2021
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Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Overexpression of the receptor tyrosine kinase MET has been linked to poor survival in several cancer types, and MET has been suggested to interact with stem cell networks. In vitro studies have further suggested a possible benefit of a combined treatment using PARP and MET inhibitors. We used a tissue microarray (TMA) with 130 samples of advanced-stage high-grade serous fallopian tube/ovarian cancer (HGSC) to investigate the prognostic value of MET protein expression alone and in combination with the stem cell factor SOX2. The possible synergistic effects of a PARP and MET inhibitor treatment were evaluated in two cell lines with BRCA1 or BRCA2 deficiency and in their BRCA1/2-proficient counterparts. Patients with tumors positive for MET had worse overall survival (log-rank test, p = 0.015) compared to patients with MET-negative tumors. The prognostic role of MET was even more prominent in the subgroup of patients with SOX2-negative tumors (p = 0.0081). No synergistic effects of the combined treatment with PARP and MET inhibitors were found in the cell lines examined. We conclude that MET expression could be used as a marker for OS in HGSC and that stemness should be taken into consideration when evaluating the mechanisms of this effect.
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| 16. |
- Darlin, Lotten, et al.
(författare)
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The sentinel node concept in early cervical cancer performs well in tumors smaller than 2 cm.
- 2010
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 117:2, s. 266-269
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of the study was to evaluate the sentinel node (SLN) concept for lymphatic mapping in early stage cervical cancer. METHODS: 105 women with early stage (1a1-2a) cervical cancer were scheduled for the sentinel node procedure in conjunction with a complete pelvic lymphadenectomy. The day before surgery, 1-1.5 mL 120MBq Tc(99) albumin nanocolloid was injected submucosally at four points around the tumor followed by a lymphoscintigram (LSG) to achieve an overview of the radiotracer uptake. RESULTS: During surgery, the overall detection rate (gamma probe) of at least one SLN was 90% (94/105 women) whereas at least one SLN was identified in 94% (61/65 women) with a tumor 2 cm) node without radiotracer uptake. The negative predictive value for patients with cervical cancers
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| 17. |
- Epstein, E., et al.
(författare)
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Gray-scale and color Doppler ultrasound characteristics of endometrial cancer in relation to stage, grade and tumor size
- 2011
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Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 38:5, s. 586-593
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To describe the gray-scale and vascular characteristics of endometrial cancer in relation to stage, grade and size using two-dimensional (2D)/three-dimensional (3D) transvaginal ultrasound. Methods This was a prospective multicenter study including 144 women with endometrial cancer undergoing transvaginal ultrasound before surgery. The sonographic characteristics assessed were echogenicity, endometrial/myometrial border, fibroids, vascular pattern, color score and tumor/uterus anteroposterior (AP) ratio. Histological assessment of tumor stage, grade, type and growth pattern was performed. Results Hyperechoic or isoechoic tumors were more often seen in Stage IA cancer, whereas mixed or hypoechoic tumors were more often found in cancers of Stage IB or greater (P = 0.003). Hyperechogenicity was more common in Grade 1-2 tumors (i.e. well or moderately differentiated) (P = 0.02) and in tumors with a tumor/uterine AP ratio of <50% (P = 0.002), whereas a non-hyperechoic appearance was more commonly found in Grade 3 tumors (i.e. poorly differentiated) and in tumors with a tumor/uterine AP ratio of >= 50%. Multiple global vessels were more often seen in tumors of Stage IB or greater than in Stage IA tumors (P = 0.02), in Grade 3 tumors than in Grade 1 and 2 tumors (P = 0.02) and in tumors with a tumor/uterine AP ratio of >= 50% (P < 0.001). A moderate/high color score was significantly more common in tumors of higher stage (P = 0.03) and larger size (P = 0.001). Conclusion The sonographic appearance of endometrial cancer is significantly associated with tumor stage, grade and size. More advanced tumors often have a mixed/hypoechoic echogenicity, a higher color score and multiple globally entering vessels, whereas less advanced tumors are more often hyperechoic and have no or a low color score. Copyright (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd.
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| 18. |
- Epstein, Elisabeth, et al.
(författare)
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Sonographic characteristics of squamous cell cancer and adenocarcinoma of the uterine cervix.
- 2010
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Ingår i: Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. - : Wiley. - 1469-0705. ; Apr 8, s. 512-516
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To describe the sonographic characteristic of squamous cell cancer (SCC) and adenocarcinoma (AC) of the cervix using transvaginal ultrasound. METHODS: Women with early stage cervical cancer undergoing transvaginal ultrasound examination prior to surgery were prospectively included. The sonographic characteristics were assessed with regard to tumor morphology, vascularization, size, extension and location. Histological assessment of tumor subtype, size, growth pattern, extension, location was performed. Both sonographic and histological assessments were done according to a standardized protocol. RESULTS: Fifty-five women were recruited. Ten were excluded since no tumor was seen on ultrasound and 5 because radical surgery was aborted due to positive lymph nodes, detected by the sentinel node technique. Among the remaining 40 women 20 had AC and 20 SCC. At pathological examination 34 women had tumors confined to the cervix, 3 had parametrial and 3 vaginal invasion. Hypoechoic echogenicity was associated with SCC in 73% (11/15), while isoechoic echogenicity indicated AC in 68% (13/19) of the women (p=0.03). Mixed echogenicity (n=4) showed a non-significant relation to larger tumor volume (p=0.23). Hyperechoic echogenicity was found in 2 women, both with the less malignant villoglandular AC. Color Doppler signals were found in all AC and 90% (18/20) of the SCC, as compared to most normal cervical tissue with virtually no detectable vascularization. CONCLUSIONS: We found that the sonographic appearance of SCC and AC differs, a knowledge that can be of use in the clinical evaluation of cervical tumors. Copyright (c) 2010 ISUOG. Published by John Wiley & Sons, Ltd.
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| 19. |
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| 20. |
- Harbst, Katja, et al.
(författare)
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Multiple metastases from cutaneous malignant melanoma patients may display heterogeneous genomic and epigenomic patterns.
- 2010
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Ingår i: Melanoma Research. - 0960-8931. ; 20:5, s. 381-391
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Tidskriftsartikel (refereegranskat)abstract
- Disseminated melanoma is an aggressive disease with fatal outcome. Better understanding of the underlying biology is needed to find effective treatment. We applied microarray-based comparative genomic hybridization, gene expression and CpG island methylation analysis of primary tumors and multiple metastases from five melanoma patients with the aim of analyzing the molecular patterns of melanoma progression. Epigenetic profiling showed that the multiple metastases after a single primary melanoma share similar methylation patterns for many genes, although differences in methylation between the lesions were evident for several genes, example, PTEN, TFAP2C, and RARB. In addition, DNA copy number and global gene expression profiles of tumors from individual patients were highly similar, confirming common origin of metastases. Some of the identified genomic aberrations, for example, gain of chromosome 6p and loss of chromosomes 6q and 10, persisted during progression, indicating early changes highly important for melanoma development. Homozygous deletions at 3p26.1 and 6q23.2-q23.3 appeared in two consecutive metastases originating from the same primary tumor, respectively, in a mutually exclusive manner that provides evidence for two genetically different subclones. However, in another case, the similarity of the copy number aberrations in subsequent metastatic lesions suggests sequential metastatic development through the clonal evolution. These data are further corroborated by a switch in CDH1 and CDH2 expression between metastases from the same patient. In conclusion, our results provide evidence for different models of metastatic progression in melanoma.
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| 21. |
- Hardell, Elin, et al.
(författare)
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Validation of a Mitotic Index Cutoff as a Prognostic Marker in Undifferentiated Uterine Sarcomas
- 2017
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Ingår i: American Journal of Surgical Pathology. - 0147-5185 .- 1532-0979. ; 41:9, s. 1231-1237
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Tidskriftsartikel (refereegranskat)abstract
- Undifferentiated uterine sarcomas (UUS) are a heterogenous group of high-grade mesenchymal tumors. Although these tumors are highly aggressive, a subset of patients may experience long-term survival. These tumors have previously been divided morphologically into uniform and pleomorphic types. A previous study demonstrated that a mitotic index cutoff of 25 mitoses/10 high-power fields (corresponding to 11.16 mitotic figures/mm) could successfully divide tumors into 2 prognostic groups with significantly different overall survival. The goals of the current study were to (1) validate this mitotic index cutoff in an independent, multicenter cohort and (2) explore the prognostic value of the mitotic index groups in relation to other clinicopathologic variables. Cases were included from 3 independent institutions: The Norwegian Radium Hospital, The Mayo Clinic, and Skåne University Hospital. A total of 40 tumors were included after central review. All cases were negative for the YWHAE-FAM22A/B and JAZF1-JJAZ1 translocations. Survival data were available on all patients. In this study, one-third of patients with UUS survived beyond 5 years. The crude (unadjusted) Cox Proportional Hazards model revealed a number of parameters that significantly impacted overall survival, including mitotic index group, patient age, stage, and the presence of tumor necrosis. Classification into the uniform and pleomorphic types was not prognostic. Combining these parameters into an adjusted model revealed that only the mitotic index group and stage were prognostic. On the basis of these findings, it is proposed that UUS be subdivided into “mitogenic” and “not otherwise specified” types.
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| 22. |
- Jönsson, Jenny-Maria, et al.
(författare)
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Distinct gene expression profiles in ovarian cancer linked to Lynch syndrome.
- 2014
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Ingår i: Familial Cancer. - : Springer Science and Business Media LLC. - 1389-9600 .- 1573-7292. ; 13:4, s. 537-545
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian cancer linked to Lynch syndrome represents a rare subset that typically presents at young age as early-stage tumors with an overrepresentation of endometrioid and clear cell histologies. We investigated the molecular profiles of Lynch syndrome-associated and sporadic ovarian cancer with the aim to identify key discriminators and central tumorigenic mechanisms in hereditary ovarian cancer. Global gene expression profiling using whole-genome c-DNA-mediated Annealing, Selection, extension, and Ligation was applied to 48 histopathologically matched Lynch syndrome-associated and sporadic ovarian cancers. Lynch syndrome-associated and sporadic ovarian cancers differed by 349 significantly deregulated genes, including PTPRH, BIRC3, SHH and TNFRSF6B. The genes involved were predominantly linked to cell growth, proliferation, and cell-to-cell signaling and interaction. When stratified for histologic subtype, hierarchical clustering confirmed distinct differences related to heredity in the endometrioid and serous subtypes. Furthermore, separate clustering was achieved in an independent, publically available data set. The distinct genetic signatures in Lynch syndrome-associated and sporadic ovarian cancers point to alternative preferred tumorigenic routes and suggest that genetic discriminators may be relevant for molecular diagnostics and targeted therapeutics.
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| 23. |
- Jönsson, Jenny Maria, et al.
(författare)
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Homologous recombination repair mechanisms in serous endometrial cancer
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Serous endometrial cancer (SEC) resembles high-grade serous ovarian cancer (HGSOC) genetically and clinically, with recurrent copy number alterations, TP53 mutations and a poor prognosis. Thus, SEC patients may benefit from targeted treatments used in HGSOC, e.g., PARP inhibitors. However, the preclinical and clinical knowledge about SEC is scarce, and the exact role of defective DNA repair in this tumor subgroup is largely unknown. We aimed to outline the prevalence of homologous recombination repair deficiency (HRD), copy-number alterations, and somatic mutations in SEC. OncoScan SNP arrays were applied to 19 tumors in a consecutive SEC series to calculate HRD scores and explore global copy-number profiles and genomic aberrations. Copy-number signatures were established and targeted sequencing of 27 HRD-associated genes was performed. All factors were examined in relation to HRD scores to investigate potential drivers of the HRD phenotype. Ten of the 19 SEC tumors (53%) had an HRD score > 42, considered to reflect an HRD phenotype. Higher HRD score was associated with loss of heterozygosity in key HRD genes, and copy-number signatures associated with non-BRCA1/2 dependent HRD in HGSOC. A high number of SECs display an HRD phenotype. It remains to be elucidated whether this also confers PARP inhibitor sensitivity.
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| 24. |
- Jönsson, Jenny-Maria, et al.
(författare)
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Molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes.
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:9
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Tidskriftsartikel (refereegranskat)abstract
- Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities with the well-established intrinsic molecular subtypes of breast cancer.
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| 25. |
- Jönsson, Jenny-Maria, et al.
(författare)
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Sex Steroid Hormone Receptor Expression Affects Ovarian Cancer Survival.
- 2015
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Ingår i: Translational Oncology. - : Elsevier BV. - 1936-5233. ; 8:5, s. 424-433
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Tidskriftsartikel (refereegranskat)abstract
- Although most ovarian cancers express estrogen (ER), progesterone (PR), and androgen (AR) receptors, they are currently not applied in clinical decision making. We explored the prognostic impact of sex steroid hormone receptor protein and mRNA expression on survival in epithelial ovarian cancer.
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| 26. |
- Lindahl, Bengt, et al.
(författare)
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Adenocarcinoma Corpus Uteri Stage I-II : Results of a Treatment Programme Based upon Cytometry
- 2009
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 29:11, s. 4731-4735
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Tidskriftsartikel (refereegranskat)abstract
- The results of a treatment method on adenocarcinoma corpus uteri stage I-II based upon cytometrically measured DNA ploidy are presented. All patients had a simple hysterectomy. Adjuvant treatment (postoperative vaginal brachytherapy) were given only, to those patients with non-diploid tumours regardless of stage and grade. A total of 1,634 women with endometroid adenocarcinoma corpus uteri stage I-II were included where 1,396 patients were followed-up for at least 5 years or until death and the remaining 238 patients were followed-up 3.5-5 years or until death. By using cytometry only, we identified a low-risk group comprising 83% of the patients (with 52% dead from their disease) and a high-risk group of 17% (with 15.7% dead from their disease). By using grade only (well- and moderately differentiated vs poorly differentiated), the low-risk group comprised 87% of the patients (with 4.6% dead from their disease) and the high-risk group 13% (with 13% dead from their disease). By using stage only (stage Ia and Ib vs stage Ic and II), the low-risk group comprised 78% of the patients (with 3.6% dead from their disease) and the high risk group 22% (with 14.5% dead from their disease). By combining these prognostic parameters, we were able to identify small subgroups with increased mortality rates in need of adjuvant therapy. As ploidy still had a strong prognostic strength regardless of given adjuvant radiotherapy, we do not believe that this treatment was effective. We therefore recommend future research to be directed toward cytostatics as an alternative adjuvant treatment.
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| 27. |
- Martin de la Fuente, Laura, et al.
(författare)
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Copy number signatures for early diagnosis of high-grade serous ovarian carcinoma
- 2022
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundThe detection of ovarian carcinoma-derived somatic mutations in cervical samples and uterine lavages in several studies since 2013, has brought hope for the development of new biomarkers for early detection. High-grade serous ovarian carcinoma (HGSC) is strongly dominated by copy number alterations (CNAs). These CNAs are the consequence of underlying mutational processes in HGSC. We interrogated CNAs from low coverage whole-genome sequencing (WGS) data in HGSC tumors, plasma, endometrial biopsies, and cervical samples to explore if copy number signatures can be used as a biomarker for early detection of HGSC.Methods A total of 204 samples were included from 18 patients with HGSC, four BRCA mutation carriers and seven benign controls. Estimations of ploidy and cellularity, and thus calculation of absolute copy number, were optimized through a combination of the ACE, Rascal, and ichorCNA bioinformatic tools. Mixture modelling was used to subgroup the six fundamental copy number features and non-negative matrix factorization was used to generate the signatures and cluster the samples.ResultsWe extracted six fundamental copy number features from 69 diagnostic and pre-diagnostic cervical samples from patients diagnosed with HGSC and generated six CN signatures. We found different distributions of features in benign samples compared to tumors and cervical samples from HGSC patients. We also observed different exposures to the six signatures in different patient groups.ConclusionsFurther understanding of the components and cell types contributing to each signature, and inclusion of more cervical samples into the approach, will hopefully identify a novel tumorigenic signature for early detection of HGSC in cervical samples.
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| 28. |
- Martin de la Fuente, Laura, et al.
(författare)
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PD-1/PD-L1 expression and tumor-infiltrating lymphocytes are prognostically favorable in advanced high-grade serous ovarian carcinoma
- 2020
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Ingår i: Virchows Archiv: an international journal of pathology. - : Springer Science and Business Media LLC. - 1432-2307. ; 477:1, s. 83-91
-
Tidskriftsartikel (refereegranskat)abstract
- The response rate to checkpoint inhibitors for women with high-grade serous carcinoma of the ovary, fallopian tube, and peritoneum (HGSC) is modest, and development of predictive biomarkers is needed. The main focus has been on tumor cell PD-L1 expression, but its assessment alone is insufficient for patient selection in most malignancies. We mapped the presence of macrophages (CD68 and CD163) and lymphocytes (CD3) located within the tumor epithelium, the cell type-specific expression of PD-L1 and PD-1, and their impact on 5-year overall survival (OS) in a consecutive cohort of 130 women diagnosed with advanced HGSC between 2011 and 2015. PD-L1 was expressed mainly by macrophages (not by tumor cells) and PD-1 by lymphocytes. Women with higher CD3, PD-L1, and PD-1 expression had improved OS (P = 0.03, P = 0.007, and P = 0.02, respectively). In the external data set (203 women), high expression of CD274 (encoding PD-L1) was associated with improved OS (P = 0.03), in accordance with our results. Furthermore, higher CD163 expression was associated with better outcome in women with no residual tumor after primary surgery (P = 0.02). Thus, women with greater lymphocyte tumor infiltration had better outcome and PD-L1/PD-1 expression, regardless of PD-1/PD-L1 being markers for immune suppressive pathways, conferred a survival benefit in our cohort. Our results highlight that tumor immunity may be harnessed in subsets of HGSC.
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| 29. |
- Måsbäck, Anna, et al.
(författare)
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Clinical and histopathological features of malignant melanoma in germline CDKN2A mutation families
- 2002
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Ingår i: Melanoma Research. - 0960-8931. ; 12:6, s. 549-557
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Tidskriftsartikel (refereegranskat)abstract
- Primary cutaneous malignant melanomas (CMMs) from 26 individuals belonging to nine families with an identified CDKN2A mutation were clinically and histopathologically compared with 78 matched CMM controls and with a population-based series of CMMs (n=667). All tumours were histopathologically re-examined. CDKN2A-associated cases were significantly less invasive compared with the matched controls, with an adjusted odds ratio (adjOR) of 2.9 and a 95% confidence interval (CI) of 1.0-8.1 (P=0.04). According to the odds ratio (OR) values, CDKN2A-associated cases seemed to have tumours more often located on the head and neck (adjOR 2.9, 95% CI 0.6-13.7), with less inflammation (adjOR 0.7, 95% CI 0.3-1.8) and regression (adjOR 0.6, 95% CI 0.2-1.8) but more frequent histological ulceration (adjOR 1.9, 95% CI 0.6-5.8). In comparison with the population-based material, CDKN2A-associated cases were significantly younger at diagnosis (crude OR 3.5, 95% CI 1.6-7.5, divided at 50 years) and had less regressive reaction in their tumours (crude OR 0.355 95% CI 0.2-0.8). No significant differences were seen for tumour thickness between the different groups. On multivariate analysis, the overall survival was significantly worse for thicker tumours and older age (P=0.04 for both). To our knowledge this is the first description of the histopathological features of CMMs from families with mutations in the CDKN2A gene.
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| 30. |
- Måsbäck, Anna, et al.
(författare)
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Cutaneous malignant melanoma in South Sweden 1965, 1975, and 1985. A histopathologic review
- 1994
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Ingår i: Cancer. - 0008-543X. ; 73:6, s. 1625-1630
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Tidskriftsartikel (refereegranskat)abstract
- Background. There is an increase in the incidence of cutaneous malignant melanoma (CMM) among white people throughout the world. In Sweden, a fivefold increase has been recorded since 1960, but the mortality is rising at a much lower rate. Tumor thickness is the single most important prognostic factor for primary melanoma. This study aimed to clarify whether the thickness of the tumor in invasive CMM decreased during the period 1965–1985. Methods. This population‐based study identified 574 cases of CMM, both invasive and noninvasive, in the South Swedish Health Care Region in 1965, 1975, and 1985. Twenty‐six cases were excluded because the collection or evaluation of the material was not possible. The remaining 548 cases were reviewed histopathologically, and a diagnosis of invasive CMM was rejected in 71 cases. Eventually, 467 cases of invasive melanoma remained in our study (70 in 1965, 124 in 1975, and 273 in 1985). The level of invasion, tumor thickness, regression, ulceration, presence of inflammatory cells, benign naevus cells, and the site of presentation were studied. Results. The study found neither a significant decrease of tumor thickness of invasive CMM nor changes in the level of invasion or proportion of ulcerated melanoma. A significantly higher proportion of melanoma tumors containing benign naevus cells was seen throughout the years (P < 0.05). Women had significantly fewer inflammatory cells in their tumors than did men (P < 0.01). As expected, the anatomical site of presentation showed a significant sex‐related difference, with more tumors on the legs of female patients and more on the trunk of male patients (P < 0.001). Conclusions. There is a divergence between the rapidly increasing incidence and the slower increase in mortality of CMM. This cannot be explained by a removal of the melanoma at a thinner thickness. Differences between the sexes according to the tumor site and the increasing rate of CMM containing benign naevus cells could implicate changes in the tumor biology. Public education in Sweden concerning ultraviolet radiation and the connection with melanoma is fairly new and might not have any influence on this time period. Additional investigation is needed to clarify this matter.
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| 31. |
- Måsbäck, Anna
(författare)
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Malignant Melanoma in southern Sweden; Histopathology, Prognosis and Aetiology
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose was to study the prognostic and aetiologic risk factors for melanoma in correlation to histopathology. Paper 1-3: Thin tumours (<0.8 mm), tumours with inflammation and median age at diagnosis were signifcantly increasing in 711 CMM patients during the period 1965-89. No difference was found in median thickness. Factors that significantly improved prognosis were; thin tumour thickness, absence of ulceration, female gender, tumour location on extremities, young age and moderate/much tumour inflammation. Correlations between different factors were found, e.g. tumour localisation predominating on the back in males and on the legs in females. LMM (Lentiginous Malignant Melanoma) was seen in combination of old age and facial tumour site. Further there was a relation between thicker tumours and deeper invasion, nodular type (NM), ulceration and older age. Tumours with inflammation were related to thinner tumours, younger age, male sex, location on non-extremities and absence of naevus cells. Paper 4: In a case-control study including 366 CMM patients, a history of melanoma in the family was significantly related to thin tumours (<0.8 mm), tumour site on the trunk and non-significantly associated to younger age at diagnosis. Further the risk for developing SSM-type was significantly increased with the tendency to freckle, raised naevi, propensity to sunburn and decreased with out-door occupation. The NM-type was associated with the presence of raised naevi on the forearm and to sunburn. Absence of naevus cells in the tumour had a significant correlation to sunburn and the presence of raised naevi. Paper 5: From families with CDKN2A-mutation 26 CMM patients were identified and matched with each 3 controls. The invasive level according to Clark was significantly lower among cases compared to controls. No significant differences were seen for tumour thickness. Compared to a population-based material (n=667), cases were significantly younger at diagnosis (median age 42 vs. 61 years) and had less regressive reaction in their tumours.
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| 32. |
- Måsbäck, Anna, et al.
(författare)
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Problems in assessing multiple cutaneous melanoma. A review on the accuracy of a population based cancer registry.
- 2010
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Ingår i: Cancer Epidemiology. - : Elsevier BV. - 1877-7821. ; 34, s. 262-266
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Tidskriftsartikel (refereegranskat)abstract
- Databases with information on malignant tumors are of great value for epidemiologic studies. From the Regional South Swedish Tumour Registry, which is of documented high quality, 24 patients out of 8008 with reported melanoma diagnosis 1973-2003 were reported as having multiple (>/=3) primary, invasive cutaneous malignant melanomas (CMM). Of the 76 tumours identified in these patients, 7 (9%) were found not to be invasive melanomas. Additional cases could be put into question since the lesions could be interpreted as epidermotropic metastases, a diagnosis which can be difficult to establish reliably by microscopic examination. Among the 24 patients we could also identify 8 (10%) additional lesions representing invasive CMM, not included in the Tumour Registry database. Thorough information concerning an earlier melanoma diagnosis and its site of presentation is needed from the clinician and the pathologist for optimal assessment of the histology and the prognostication of the patient, as well as proper reporting to a tumour registry. Identifying multiple primary malignant melanomas is also of special importance for counselling patients belonging to families with hereditary disease. In this study it is shown that diagnosing and reporting multiple malignant melanomas can be problematic due to insufficient communication and to the rare and deceptive capability of cutaneous metastases to imitate primary tumours.
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| 33. |
- Måsbäck, Anna, et al.
(författare)
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Prognostic factors in invasive cutaneous malignant melanoma: a population-based study and review
- 2001
-
Ingår i: Melanoma Research. - 0960-8931. ; 11:5, s. 435-445
-
Tidskriftsartikel (refereegranskat)abstract
- A population-based study from Sweden identified 711 patients with cutaneous malignant melanoma diagnosed in 1965, 1975, 1985 and 1989. Prognostic factors were evaluated and a review of the literature was performed. On univariate analysis, thick tumours (> 0.8 mm) (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.6-2.1), increasing Clark level (OR 1.8, 95% CI 1.6-2.0), ulceration (OR 1.8, 95% CI 1.6-2.0), nodular melanoma (OR 1.5, 95% CI 1.3-1.6) and increasing age (continuous variable, P < 0.0001) were associated with a shorter survival. Location on extremities (OR 0.8, 95% CI 0.7-0.9), inflammation (OR 0.8, 95% CI 0.7-0.9) and female gender (OR 0.8, 95% CI 0.8-0.9) were associated with improved survival. On multivariate analysis, thick tumours (> 0.8 mm) (OR 1.5, 95% CI 1.2-1.7) and ulceration (OR 1.4, 95% CI 1.2-1.6) were independently related to a poor prognosis, while location on extremities (OR 0.8, 95% CI 0.7-0.9), inflammation (OR 0.8, 95% CI 0.7-0.9) and female gender (OR 0.8, 95% CI 0.8-1.0) were associated with improved survival. No difference in mean tumour thickness was seen over time, but there was a significant increase in the percentage of thin melanomas (< 0.8 mm) in 1985 (P = 0.01) and 1989 (P = 0.002) compared with 1965. The incidence of melanomas with inflammation increased significantly (P = 0.04), as did age at diagnosis (P = 0.005).
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| 34. |
- Nastic, Denis, et al.
(författare)
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A Selective Biomarker Panel Increases the Reproducibility and the Accuracy in Endometrial Biopsy Diagnosis
- 2017
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Ingår i: International Journal of Gynecological Pathology. - : LIPPINCOTT WILLIAMS & WILKINS. - 0277-1691 .- 1538-7151. ; 36:4, s. 339-347
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Tidskriftsartikel (refereegranskat)abstract
- Grading and histologic typing of endometrial cancer in biopsy material has a direct impact on the decision to perform lymphadenectomy and/or omentectomy in many cancer centers. Endometrial biopsies are among the most common general surgical pathology specimens. Multiple studies have shown that biopsy diagnosis suffers from a lack of reproducibility. Although many biomarkers have been proposed, none have been demonstrated to improve the diagnosis in the biopsy setting. In this study, 70 biopsies with endometrial carcinoma were supplemented with a biomarker panel consisting of ER, PR, P53, and DNA ploidy. A representative H&E slide was scanned digitally and made available to 12 gynecologic pathologists in 4 Nordic countries: Finland, Denmark, Sweden, and Norway. Reviewers diagnosed the cases both before and after being provided with the biomarker results. The interobserver percent agreement and Cohen κ improved from 75.8% (κ=0.52, moderate) to 84% (κ=0.68, substantial) with inclusion of the biomarker panel. Agreement with the subsequent hysterectomy diagnosis also improved from 83.6% (κ=0.67) to 88.7% (κ=0.77). There was no statistical improvement between a reflex (84% agreement) and a reflective testing algorithm (82.9% agreement), suggesting that the selective use of biomarkers is appropriate. Difficult cases were almost exclusively high-grade tumors. Finally, a statistical model indicated that only P53 and DNA ploidy, in conjunction with an H&E review, had an impact on the decision to upgrade or downgrade cases.
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| 35. |
- Nielsen, Kari, et al.
(författare)
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A prospective, population-based study of 40000 women regarding host factors, UV exposure and sunbed use in relation to risk and anatomic site of cutaneous melanoma.
- 2012
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 131:3, s. 706-715
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Tidskriftsartikel (refereegranskat)abstract
- Prospective cohort studies about cutaneous melanoma (CM) risk are still few. Host factor- and UVR exposure data were collected prospectively by questionnaire in this population-based cohort study including 40000 Swedish born women, aged 25-64 years at enrolment (1990). Risk for CM (Cox regression and Stepwise Cox regression [SCR], hazard ratios [HRs] with 95 % Confidence Intervals [CI]) in relation to risk factors, age groups (older or younger than 40 years) and primary site, were analysed. In 29520 women with complete follow-up through 2007, 155 invasive and 60 in situ CM were recorded. High numbers of nevi (HR, 2.9; 95% CI, 1.7-5.0) and heredity (HR, 3.7; 95% CI, 2.0-6.8) were associated with risk for CM. SCR analysis added red hair as a risk factor. Sunbed use >10 times/year increased risk for women <40 y (HR, 2.5; 95% CI, 1.0-6.2) and a trend for risk associated with sunbathing vacations (HR, 1.4; 95% CI, 1.0-2.0) was shown for women >40 y. Trunk melanoma showed correlations with high numbers of nevi (HR, 3.0; 95% CI, 1.2-7.3) and heredity (HR, 3.2; 95% CI, 1.1-9.4). Head/neck site was correlated to sunbathing vacations (HR, 2.5; 95% CI, 1.2-5.3) and heredity (HR, 7.6; 95% CI, 1.8-31.8). Our study supports divergent etiologic pathways to CM, with high numbers of nevi correlated to increased risk for trunk CM. Furthermore, it confirms that high numbers of nevi, red hair and heredity for CM are the most important risk factors and frequent sunbed use might be a risk factor for younger women. © 2011 Wiley-Liss, Inc.
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| 36. |
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| 37. |
- Nielsen, Kari, et al.
(författare)
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Swedish CDKN2A mutation carriers do not present the atypical mole syndrome phenotype.
- 2010
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Ingår i: Melanoma Research. - 0960-8931. ; Jul 1, s. 266-272
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Tidskriftsartikel (refereegranskat)abstract
- Phenotypic characteristics were examined in melanoma-prone southern Swedish CDKN2A (p16-113insArg/p14ARF-128insSer) mutation families, in relation to the CDKN2A genotype, nevi, clinically atypical nevi (CAN) and melanoma. Individuals from eight melanoma-prone families, with index patients carrying the CDKN2A mutation, were offered skin examinations and genotyping (CDKN2A and MC1R). Ninety-three individuals above 18 years of age participated; 29 invasive melanomas in 16 patients were recorded, all in the 38 verified CDKN2A mutation carriers. Median age at diagnosis was 36 years. Several MC1R variants were observed. A significant correlation to CAN (P=0.01) and red hair colour (P=0.02) could be confirmed in melanoma patients. A positive mutation status (CDKN2A) was correlated to one or more CAN (P=0.007) but neither to blue eyes, red hair colour, heavy freckling nor high number of nevi. For mutation carriers, median total naevus count was 24 and interquartile range was 12-47 (mean 31); whereas for the whole cohort, median total naevus count was 12 and interquartile range was 5-25 (mean 22). No participant fulfilled the atypical mole syndrome phenotype criteria. Melanomas were diagnosed only in mutation carriers, and melanoma diagnosis was statistically correlated to the presence of one or more CAN and red hair colour, supporting the possible synergistic effect of a MC1R mutation on increased risk of melanoma in patients with a CDKN2A mutation. Family history, with verified tumour diagnoses, remains an important clinical tool for finding mutation carriers for referral to clinical geneticists and simultaneous presence of CAN in probable mutation carriers might strengthen this indication. The atypical mole syndrome phenotype was, however, not verified in the studied families and total naevus counts were low.
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| 38. |
- Persson, Jan, et al.
(författare)
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Description of a reproducible anatomically based surgical algorithm for detection of pelvic sentinel lymph nodes in endometrial cancer
- 2017
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258. ; 147:1, s. 120-125
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe and evaluate a reproducible, anatomically based surgical algorithm, including reinjection of tracer to enhance technical success rate, for detection of pelvic sentinel lymph nodes (SLNs) in endometrial cancer (EC). Methods: A prospective study of 102 consecutive women with high risk EC scheduled for robotic surgery was conducted. Following cervical injection of a fluorescent dye, an algorithm for trans- and retroperitoneal identification of tracer display in the lower and upper paracervical pathways was strictly adhered to. To enhance the technical success rate, this included ipsilateral reinjection of tracer in case of non-display of any lymphatic pathway. The lymphatic pathways were kept intact by opening the avascular planes. To minimize disturbance from leaking dye, removal of SLNs was first performed along the lower paracervical (presacral) pathways followed by the more caudal upper paracervical pathways. In each pathway, the juxtauterine node with an afferent lymph vessel was defined as an SLN. After removal of SLNs, a complete pelvic and, unless contraindicated, infrarenal paraaortic lymph node dissection was performed. Results: The bilateral detection rate including tracer reinjection was 96%. All 24 (23.5%) node positive patients had at least one metastatic SLN. Presacral lymph node metastases were discovered in 33.3% of the node positive patients. One patient (4.2%) had an isolated presacral lymph node metastasis. Conclusions: The described cranial-to-caudal anatomically based surgical SLN algorithm, including a presacral dissection and reinjection of tracer, results in a high SLN detection rate and identified all patients with lymph node metastases.
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| 39. |
- Persson, Jan, et al.
(författare)
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Histopathology indicates lymphatic spread of a pelvic retroperitoneal ectopic pregnancy removed by robot-assisted laparoscopy with temporary occlusion of the blood supply.
- 2010
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; APR 8, s. 835-839
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Retroperitoneal ectopic pregnancies are extremely rare and a diagnostic and therapeutic challenge as an early diagnosis is difficult and all treatments entail a risk for severe bleeding. We present a case of a live completely retroperitoneal ectopic pregnancy in the right obturator fossa. Following 3D color Doppler vaginal ultrasonography to evaluate the relation to larger blood vessels the pregnancy was completely removed by robot-assisted laparoscopic surgery. The hypogastric artery was temporarily occluded by removable vessel clips. Time for surgery was 126 minutes, no bleeding occurred. The postoperative course was uneventful and s-betahCG normalized in five weeks. Histopathology of the intact specimen showed trophoblast surrounded by lymphatic tissue. We believe robot-assisted laparoscopic surgery is a feasible and safe technique for surgery of retroperitoneal ectopic pregnancies with similar or other locations allowing occlusion of the main supplying artery. Lymphatic spread may explain retroperitoneal ectopic pregnancies.
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| 40. |
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