| 1. |
- Ketabi, Zohreh, et al.
(författare)
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Ovarian cancer linked to lynch syndrome typically presents as early-onset, non-serous epithelial tumors
- 2011
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 121:3, s. 462-465
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Heredity is a major cause of ovarian cancer and during recent years the contribution from germline mismatch repair (MMR) gene mutations linked to Lynch syndrome has gradually been recognized. Methods. We characterized clinical features, tumor morphology and mismatch repair defects in all ovarian cancers identified in Swedish and Danish Lynch syndrome families. Results. In total, 63 epithelial ovarian cancers developed at mean 48 (range 30-79) years of age with 47% being early stage (FIGO stage I). Histologically, endometrioid (35%) and clear cell (17%) tumors were overrepresented. The underlying MMR gene mutations in these families affected MSH2 in 49%, MSH6 in 33% and MLH1 in 17%. Immunohistochemical loss of the corresponding MMR protein was demonstrated in 33/36 (92%) tumors analyzed. Conclusion. The combined data from our cohorts demonstrate that ovarian cancer associated with Lynch syndrome typically presents at young age as early-stage, non-serous tumors, which implicates that a family history of colorectal and endometrial cancer should be specifically considered in such cases. (C) 2011 Elsevier Inc. All rights reserved.
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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- Asp, Mihaela, et al.
(författare)
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Prognostic Value of Peritoneal Cancer Index After Complete Cytoreductive Surgery in Advanced Ovarian Cancer
- 2022
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 1791-7530 .- 0250-7005. ; 42:5, s. 2541-2551
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Tidskriftsartikel (refereegranskat)abstract
- Background/aim: Residual disease (RD) after primary debulking surgery (PDS) is a prognostic factor for survival in advanced ovarian cancer (AOC). This study aimed to examine whether the tumor extent affects overall survival (OS) and progression-free survival (PFS) in AOC patients treated with PDS.Patients and methods: A total of 118 patients treated with PDS were included. Age, ECOG score, AOC International Federation of Gynecology and Obstetrics (FIGO) stage, CA-125, RD, peritoneal cancer index (PCI), preoperative imaging (CT-PCI) and macroscopic visualization at the surgery start (S-PCI) were analyzed. Tumor extent was quantified using the PCI, and by CT-PCI and S-PCI. Cox regression, Kaplan-Meier and receiver operating curves (ROC) were performed for survival analyses.Results: S-PCI correlated with both OS (1.067, 95%CI=1.018-1.119, p<0.007) and PFS. Patients exhibiting S-PCI≥18.5, adjusted to age, performance status, and RD, had a two-fold risk of dying (HR=2.070, 95%CI=1.061-4.038, p=0.033) compared those with PCI<18.5. CT-PCI correlated with OS in crude data (1.037, 95%CI=1.005-1.071, p=0.025), but this was not sustained in multivariate analyses. RD of any size doubled the risk of dying (2.177, 95%CI=1.235-3.838, p=0.007).Conclusion: The tumor extent at the beginning of surgery seemed to affect OS in patients with AOC, regardless of the extent of RD at the end of the surgery. PCI above 18.5 doubled the risk of dying of the disease. No difference in major complications was noted in the two groups of patients. CT-PCI seemed to play a prognostic role for PFS; however, it is still to be investigated as a prognostic factor for OS.
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| 6. |
- Asp, Mihaela, et al.
(författare)
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The role of computed tomography in the assessment of tumour extent and the risk of residual disease after upfront surgery in advanced ovarian cancer (AOC)
- 2022
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Ingår i: Archives of Gynecology and Obstetrics. - : Springer Science and Business Media LLC. - 1432-0711.
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Tidskriftsartikel (refereegranskat)abstract
- PurposeEpithelial ovarian cancer is usually diagnosed in the advanced stages. To choose the best therapeutic approach, an accurate preoperative assessment of the tumour extent is crucial. This study aimed to determine whether the peritoneal cancer index (PCI), the amount of ascites, and the presence of cardiophrenic nodes (CPLNs) visualized by computed tomography (CT) can assess the tumour extent (S-PCI) and residual disease (RD) for advanced ovarian cancer (AOC) patients treated with upfront surgery.MethodsIn total, 118 AOC cases were included between January 2016 and December 2018 at Skåne University Hospital, Lund, Sweden. Linear regression and interclass correlation (ICC) analyses were used to determine the relationship between CT-PCI and S-PCI. The patients were stratified in complete cytoreductive surgery (CCS) with no RD or to non-CCS with RD of any size. The amount of ascites on CT (CT-ascites), CA-125 and the presence of radiological enlarged CPLNs (CT-CPLN) were analysed to evaluate their impact on estimating RD.ResultsCT-PCI correlated well with S-PCI (0.397; 95% CI 0.252–0.541; p < 0.001). The risk of RD was also related to CT-PCI (OR 1.069 (1.009–1.131), p < 0.023) with a cut-off of 21 for CT-PCI (0.715, p = 0.000). The sensitivity, specificity, positive predictive value and negative predictive value were 58.5, 70.3, 52.2 and 75.4%, respectively. CT-ascites above 1000 ml predicted RD (OR 3.510 (1.298–9.491) p < 0.013).ConclusionCT is a reliable tool to assess the extent of the disease in advanced ovarian cancer. Higher CT-PCI scores and large volumes of ascites estimated on CT predicted RD of any size.
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| 7. |
- 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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| 8. |
- Bagge, Ebba, et al.
(författare)
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Pattern of endocrine treatment for epithelial ovarian cancer in the Southeast medical region of Sweden: a population-based study
- 2019
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Ingår i: Acta Oncologica. - : TAYLOR & FRANCIS LTD. - 0284-186X .- 1651-226X. ; 58:3, s. 320-325
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Tidskriftsartikel (refereegranskat)abstract
- Aim of the study: Endocrine treatment (ET) is an alternative as salvage therapy in epithelial ovarian cancer (EOC) but the usage in routine care is unknown. We evaluated the treatment patterns and outcome of patients receiving ET for EOC in the Southeast medical region in Sweden.Method: Patients were identified through the population-based Southeast Quality Registry for gynaecological cancer. Inclusion criteria were: age 18 years, histologically verified EOC diagnosed 2000-2013, ET for 4 weeks. Coverage compared with the Swedish National Cancer Registry was 100%. Data extracted from medical records was collected by means of a study-specific Case Report Form. Last date of follow-up was February 1st, 2018. All statistics were descriptive.Results: Altogether 248 (18%) of 1414 patients were treated with ET. Most (49%) had received only one, and 34% two previous lines of chemotherapy. Time from last chemotherapy to ET was 4 months, range 0-55months. The reason for initiating ET was tumor progression (66%), chemotherapy related toxicity (29%) and maintenance (4%). Tamoxifen was prescribed in 94% of cases. Best response was partial (amp;lt; 5%) and stable disease (50%). No patient had a complete response. 194 (78%) patients received subsequent chemotherapy, of these 27% had 3-7 lines of chemotherapy. Duration of ET was a median 4 months (range 1-80 months). Median time from ET to subsequent chemotherapy was 5 months (range 0-79). The median overall survival was 45 months (range 9-173).Conclusion: In the Southeast region of Sweden, endocrine treatment for EOC was prescribed inconsistently and in various settings, usually initiated by a rising CA-125 level. Poorer documentation and irregular tumor response assessment were observed for endocrine treatment compared to chemotherapy.
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| 9. |
- Bartuma, Katarina, et al.
(författare)
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Genetic profiles distinguish different types of hereditary ovarian cancer.
- 2010
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1791-2431 .- 1021-335X. ; 24:4, s. 885-895
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Tidskriftsartikel (refereegranskat)abstract
- Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian cancer (HBOC) syndrome and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Genome-wide array comparative genomic hybridization was applied to 12 HBOC associated tumors with BRCA1 mutations and 8 HNPCC associated tumors with mismatch repair gene mutations with 24 sporadic ovarian cancers as a control group. Unsupervised cluster analysis identified two distinct subgroups related to genetic complexity. Sporadic and HBOC associated tumors had complex genetic profiles with an average 41% of the genome altered, whereas the mismatch repair defective tumors had stable genetic profiles, with an average 18% of the genome altered. Losses of 4q34, 13q12-q32 and 19p13 were overrepresented in the HBOC subset. Discriminating genes within these regions include BRCA2, FOXO1A and RB1. Gains on chromosomes 17 and 19 characterized the HNPCC tumors, but target genes herein are unknown. The results indicate that HBOC and HNPCC associated ovarian cancer develop along distinct genetic pathways and genetic profiles can thus be applied to distinguish between different types of hereditary ovarian cancer.
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| 10. |
- 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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