scholarly journals Current ideas about molecular genetic subtypes of ovarian cancer: a personalized approach and a new platform for further research

2021 ◽  
Vol 11 (11) ◽  
pp. 157-168
Author(s):  
A. Rybin
Keyword(s):  
Ovarian Cancer ◽  
Molecular Subtypes ◽  
Molecular Genetic ◽  
Consensus Algorithm ◽  
Histopathological Diagnosis ◽  
Low Grade ◽  
Ovarian Carcinomas ◽  
Altered Expression ◽  
Ovarian Cancers ◽  
Genetic Subtypes

Highly malignant ovarian cancers are a histopathological diagnosis, but can be multiple diseases at the molecular level. Research aimed at identifying molecular genetic subtypes of ovarian cancer is being conducted to find an answer to the question: can different molecular subgroups influence the choice of treatment? One of the achievements of this direction is the recognition of the dualistic theory of the origin of ovarian carcinomas with their division into High-grade and Low-grade subtypes. However, the data of sequencing of the tumor genome suggest the existence of 6 subtypes of carcinoma, including two LG and four HG subtypes. Patients of subtype C1 are characterized by a high stromal response and have the lowest survival, tumors of C2 and C4 subtypes have a higher rate of intratumoral CD3 + cells, lower stroma gene expression and better survival than C1. The mesenchymal subtype C5 is widely represented by mesenchymal cells, characterized by overexpression of N-cadherins and P-cadherins, low expression of differentiation markers and lower survival than C2 and C4. The use of a consensus algorithm to determine the subtype allows the identification of only a minority of ovarian cancers (approximately 25%). In this regard, the practical significance of this classification still requires additional research, and today it is permissible to talk about the existence of only 2-3 reproducible subtypes. It is thought that it makes sense to randomize tumors into groups with altered expression of angiogenic genes and with overexpression of immune response genes, as in the angiogenic group there is a comparison of the advantage in survival (prescribing bevacizumab improves it, and in the immune group even increases bevacizumab). Molecular subtypes with poorer survival rates (proliferative and mesenchymal) also benefit most from bevacizumab treatment. The review focuses on some advances in understanding molecular, cellular, and genetic changes related to ovarian cancers with the results achieved so far in describing molecular subtypes of ovarian cancer. The available information is the basis for planning further research.

MOLECULAR AND GENETIC SUBTYPES OF OVARIAN CANCER: PROSPECTS FOR FURTHER STUDIES

2019 ◽  
Vol 65 (1) ◽  
pp. 56-62
Author(s):  
Alisa Villert ◽  
Larisa Kolomiets ◽  
Natalya Yunusova ◽  
Yevgeniya Fesik
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Molecular Subtypes ◽  
Survival Rates ◽  
Consensus Algorithm ◽  
Histopathological Diagnosis ◽  
Low Grade ◽  
High Grade ◽  
Ovarian Carcinomas ◽  
Genetic Subtypes

High-grade ovarian carcinoma is a histopathological diagnosis, however, at the molecular level, ovarian cancer represents a heterogeneous group of diseases. Studies aimed at identifying molecular genetic subtypes of ovarian cancer are conducted in order to find the answer to the question: can different molecular subgroups influence the choice of treatment? One of the achievements in this trend is the recognition of the dualistic model that categorizes various types of ovarian cancer into two groups designated high-grade (HG) and low-grade (LG) tumors. However, the tumor genome sequencing data suggest the existence of 6 ovarian carcinoma subtypes, including two LG and four HG subtypes. Subtype C1 exhibits a high stromal response and the lowest survival. Subtypes C2 and C4 demonstrate higher number of intratumoral CD3 + cells, lower stromal gene expression and better survival than sybtype C1. Subtype C5 (mesenchymal) is characterized by mesenchymal cells, over-expression of N-cadherin and P-cadherin, low expression of differentiation markers, and lower survival rates than C2 and C4. The use of a consensus algorithm to determine the subtype allows identification of only a minority of ovarian carcinomas (approximately 25%) therefore, the practical importance of this classification requires additional research. There is evidence that it makes sense to randomize tumors into groups with altered expression of angiogenic genes and groups with overexpression of the immune response genes, as in the angiogenic group there is a comparative superiority in terms of survival. The administration of bevacizumab in the angiogenic group improves survival, while the administration of bevacizumab in the immune group even worsens the outcome. Molecular subtypes with worse survival rates (proliferative and mesenchymal) also benefit most from bevacizumab treatment. This review focuses on some of the advances in understanding molecular, cellular, and genetic changes in ovarian carcinomas with the results achieved so far regarding the formulation of molecular subtypes of ovarian cancer, however further studies are needed.

scholarly journals Clinical Utility of Real-Time Targeted Molecular Profiling in the Clinical Management of Ovarian Cancer: The ALLOCATE Study

2019 ◽  
pp. 1-18
Author(s):  
Olga Kondrashova ◽  
Gwo-Yaw Ho ◽  
George Au-Yeung ◽  
Leakhena Leas ◽  
Tiffany Boughtwood ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Real Time ◽  
Targeted Therapies ◽  
Clinical Management ◽  
Clinical Utility ◽  
Advanced Ovarian Cancer ◽  
Molecular Profiling ◽  
Molecular Testing ◽  
Low Grade ◽  
Ovarian Carcinomas

PURPOSE The ALLOCATE study was designed as a pilot to demonstrate the feasibility and clinical utility of real-time targeted molecular profiling of patients with recurrent or advanced ovarian cancer for identification of potential targeted therapies. PATIENTS AND METHODS A total of 113 patients with ovarian cancer of varying histologies were recruited from two tertiary hospitals, with 99 patient cases suitable for prospective analysis. Targeted molecular and methylation profiling of fresh biopsy and archived tumor samples were performed by screening for mutations or copy-number variations in 44 genes and for promoter methylation of BRCA1 and RAD51C. RESULTS Somatic genomic or methylation events were identified in 85% of all patient cases, with potentially actionable events with defined targeted therapies (including four resistance events) detected in 60% of all patient cases. On the basis of these findings, six patients received molecularly guided therapy, three patients had unsuspected germline cancer–associated BRCA1/ 2 mutations and were referred for genetic counseling, and two intermediate differentiated (grade 2) serous ovarian carcinomas were reclassified as low grade, leading to changes in clinical management. Additionally, secondary reversion mutations in BRCA1/ 2 were identified in fresh biopsy samples of two patients, consistent with clinical platinum/poly (ADP-ribose) polymerase inhibitor resistance. Timely reporting of results if molecular testing is done at disease recurrence, as well as early referral for patients with platinum-resistant cancers, were identified as factors that could improve the clinical utility of molecular profiling. CONCLUSION ALLOCATE molecular profiling identified known genomic and methylation alterations of the different ovarian cancer subtypes and was deemed feasible and useful in routine clinical practice. Better patient selection and access to a wider range of targeted therapies or clinical trials will further enhance the clinical utility of molecular profiling.

scholarly journals Emerging Role of Inhibin as a Biomarker for Ovarian Cancer

2005 ◽  
Vol 1 (1) ◽  
pp. 51-57 ◽  
Author(s):  
David M Robertson ◽  
Martin K Oehler
Keyword(s):  
Ovarian Cancer ◽  
Granulosa Cell ◽  
Early Stage ◽  
Clinical Stage ◽  
Survival Rates ◽  
Ovarian Carcinomas ◽  
Gynecological Malignancy ◽  
Granulosa Cell Tumors ◽  
Ovarian Cancers ◽  
Specificity And Sensitivity

Ovarian cancer is the most lethal gynecological malignancy as it is diagnosed at a late clinical stage in more than 80% of patients. The development of diagnostic tests that can detect all types of ovarian cancers with high specificity and sensitivity, and at an early stage would improve survival rates. Serum inhibin is an ovarian hormone involved in the regulation of fertility, decreasing to undetectable levels after menopause. Certain ovarian malignancies, such as mucinous carcinomas and granulosa cell tumors, continue to produce inhibin, which is detectable in serum. A test for serum inhibin has been developed which is able to diagnose granulosa cell tumors and mucinous carcinomas with high accuracy. When the inhibin assay is used in conjunction with the CA125 test, which detects epithelial ovarian carcinomas, the two tests detect the majority of ovarian cancers with high sensitivity (95%) and specificity (95%). This article discusses the application of the inhibin test in ovarian cancer.

Paradigm Shift in the Management Strategy for Epithelial Ovarian Cancer

2016 ◽  
pp. e247-e257 ◽  
Author(s):  
Keiichi Fujiwara ◽  
Jessica N. McAlpine ◽  
Stephanie Lheureux ◽  
Noriomi Matsumura ◽  
Amit M. Oza
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Paradigm Shift ◽  
Management Strategy ◽  
Clear Cell ◽  
Treatment Strategies ◽  
Low Grade ◽  
Ovarian Carcinomas ◽  
Coelomic Epithelium ◽  
Histologic Types

The hypothesis on the pathogenesis of epithelial ovarian cancer continues to evolve. Although epithelial ovarian cancer had been assumed to arise from the coelomic epithelium of the ovarian surface, it is now becoming clearer that the majority of serous carcinomas arise from epithelium of the distal fallopian tube, whereas clear cell and endometrioid cancers arise from endometriosis. Molecular and genomic characteristics of epithelial ovarian cancer have been extensively investigated. Our understanding of pathogenesis of the various histologic types of ovarian cancer have begun to inform changes to the strategies for management of epithelial ovarian cancer, which represent a paradigm shift not only for treatment but also for prevention, which previously had not been considered achievable. In this article, we will discuss novel attempts at the prevention of high-grade serous ovarian cancer and treatment strategies for two distinct entities in epithelial ovarian cancer: low-grade serous and clear cell ovarian carcinomas, which are relatively rare and resistant to conventional chemotherapy.

scholarly journals Development and Validation of a Novel 11-Gene Prognostic Model for Serous Ovarian Carcinomas Based on Lipid Metabolism Expression Profile

2020 ◽  
Vol 21 (23) ◽  
pp. 9169
Author(s):  
Mingjun Zheng ◽  
Heather Mullikin ◽  
Anna Hester ◽  
Bastian Czogalla ◽  
Helene Heidegger ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lipid Metabolism ◽  
Prognostic Model ◽  
Molecular Subtypes ◽  
Gene Signature ◽  
Functional Enrichment ◽  
Serous Ovarian Cancer ◽  
Ovarian Carcinomas ◽  
Comparable Amount ◽  
Lipid Metabolism Genes

(1) Background: Biomarkers might play a significant role in predicting the clinical outcomes of patients with ovarian cancer. By analyzing lipid metabolism genes, future perspectives may be uncovered; (2) Methods: RNA-seq data for serous ovarian cancer were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. The non-negative matrix factorization package in programming language R was used to classify molecular subtypes of lipid metabolism genes and the limma package in R was performed for functional enrichment analysis. Through lasso regression, we constructed a multi-gene prognosis model; (3) Results: Two molecular subtypes were obtained and an 11-gene signature was constructed (PI3, RGS, ADORA3, CH25H, CCDC80, PTGER3, MATK, KLRB1, CCL19, CXCL9 and CXCL10). Our prognostic model shows a good independent prognostic ability in ovarian cancer. In a nomogram, the predictive efficiency was notably superior to that of traditional clinical features. Related to known models in ovarian cancer with a comparable amount of genes, ours has the highest concordance index; (4) Conclusions: We propose an 11-gene signature prognosis prediction model based on lipid metabolism genes in serous ovarian cancer.

scholarly journals Ascitis as a unique microenvironment of tumors in ovarian cancer: interaction with prognosis and chemoresistance

2019 ◽  
Vol 6 (2) ◽  
pp. 8-20
Author(s):  
A. B. Villert ◽  
L. A. Kolomiets ◽  
N. V. Yunusova
Keyword(s):  
Ovarian Cancer ◽  
Ascitic Fluid ◽  
Tumor Tissue ◽  
Molecular Genetic ◽  
Biomarker Detection ◽  
Ovarian Carcinomas ◽  
System Parameters ◽  
Igf System ◽  
Genetic Level ◽  
Igfbp 3

The severe heterogeneity of ovarian carcinomas on the molecular genetic level is associated with the absence of specific markers of chemoresistance. At the same time, ascites is an attractive biomarker detection fluid because it is easily obtained. The review is dedicated to the latest advances in the study of components characteristics of ascitic fluid in terms of their relationship with chemoresistance. Оwn data are submitted regarding the contents of the IFR system parameters (free IGFs, as well as IGFBP-3, IGFBP-4 and PAPP-A) in ascitic fluids and tumor tissue in disseminated ovarian cancer, which show the importance of their study. It is shown that the proteins level of the IGF system substantially depend on the volume of ascitic fluid. Studying the features of ascitic fluid in ovarian cancer is directly related to the prospect of new opportunities for disseminated ovarian cancer treatment.

Differentiation of Ovarian Cancers From Borderline Ovarian Tumors on the Basis of Evaluation of Tumor Vascularity in Multi–Row Detector Computed Tomography—Comparison With Histopathology

2013 ◽  
Vol 23 (9) ◽  
pp. 1597-1602 ◽  
Author(s):  
Laretta Grabowska-Derlatka ◽  
Pawel Derlatka ◽  
Piotr Palczewski ◽  
Anna Danska-Bidzinska ◽  
Ryszard Pacho
Keyword(s):  
Computed Tomography ◽  
Ovarian Cancer ◽  
Ovarian Tumors ◽  
Borderline Tumor ◽  
Tumor Vascularity ◽  
Ovarian Carcinomas ◽  
Borderline Ovarian Tumors ◽  
Ovarian Cancers ◽  
Group A ◽  
Group B

ObjectiveThe aim of this study was to evaluate the feasibility of multi–detector row computed tomography (MDCT) in the differentiation between borderline ovarian tumors and ovarian cancer on the basis of tumor morphology and specific features of tumor vascularity in correlation with the results at pathology.MethodsA triphasic MDCT protocol was used for the analysis of tumor vascularity. The following features were taken into account: (1) The number of vessels in papillary projections, solid-tissue component, and septa (2 vs >2), (2) serpentine and chaotic configuration of vessels, (3) presence of microaneurysms, and (4) presence of arteriovenous microfistulas. Masses with at least 3 of 4 features were considered ovarian cancer (group A) and masses with 2 features or less as borderline tumor (group B). Radiological findings were compared with results of postoperative pathology.ResultsPathologic vessels were found in all 56 patients. Thirty-two patients were included in group A and 24 in group B. The results of pathology were as follows: in group A: 31 malignant tumors, including 31 ovarian carcinomas and 1 benign cystadenoma; in group B: 22 borderline ovarian tumors, 1 benign cystadenoma, and 1 ovarian cancer.ConclusionsMorphological evaluation of tumor vascularity in MDCT seems to be an efficient method of differentiating between borderline ovarian tumors and ovarian carcinomas. Because of a small number of cases in the current study, a further research seems justified to confirm our results. The presented MDCT-angiographic criteria showed high sensitivity (97%) and specificity (96%) in differentiation of borderline ovarian tumors and ovarian cancers as compared with pathology. The presented CT-angiographic criteria of malignancy showed an excellent interobserver agreement.

Functional profiling of clear cell ovarian cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5035-5035
Author(s):  
Rowan Miller ◽  
Rachel Brough ◽  
Ilirjana Bajrami ◽  
Stanley B. Kaye ◽  
Christopher J. Lord ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Throughput Screening ◽  
Clear Cell ◽  
Integral Functional ◽  
Therapeutic Targets ◽  
Molecular Profiling ◽  
Loss Of Function ◽  
Ovarian Carcinomas ◽  
Ovarian Cancers ◽  
Platinum Based Chemotherapy

5035 Background: Clear cell ovarian cancer represents up to 15% of epithelial ovarian cancers. In comparison to other subtypes, clear cell ovarian carcinomas have a poorer prognosis and are relatively resistant to standard platinum based chemotherapy. Recently, loss of function mutations in the tumour suppressor gene ARID1A were identified in up to 50% of ovarian clear cell carcinomas. We have adopted an integral functional and molecular profiling approach as a route to identify new genetic dependencies and therapeutic targets for this disease. Methods: Clear cell ovarian cancer cell lines were functionally profiled using high throughput screening with chemical and siRNA libraries. This has been integrated with molecular profiling data generated from exome and transcriptome sequencing to aid the discovery of novel targets. Results: Using functional screens we have now identified critical gene dependencies and potential therapeutics in a series of clear cell ovarian cancer models. The comparison of functional viability profiles for models characterized by ARID1A loss of function mutations is now enabling an analysis of synthetic lethal effects that could be used to target clear cell ovarian cancers carrying these mutations. Conclusions: The work undertaken so far provides the framework for the discovery of therapeutic targets for clear cell ovarian cancer using an integrated approach. Revalidation of these preliminary results is now underway to characterize new genetic dependencies for this disease.

scholarly journals CLINICOPATHOLOGICAL CHARACTERISTICS OF PATIENTS WITH SYNCHRONOUS PRIMARY OVARIAN AND ENDOMETRIAL CANCERS

2016 ◽  
Vol 2 (2) ◽  
Author(s):  
Samreen Chaudary ◽  
Tabina Sadaf ◽  
Sumera Butt ◽  
Aamir Ali Syed ◽  
Neelam Siddiqui
Keyword(s):  
Ovarian Cancer ◽  
Endometrial Cancer ◽  
Clinicopathological Characteristics ◽  
Stage I ◽  
Stage Iii ◽  
Serous Carcinoma ◽  
Research Centre ◽  
Low Grade ◽  
Ovarian Cancers ◽  
Endometrial Cancers

Purpose: Synchronous primary endometrial and ovarian cancers are infrequent. The objective of this study is to evaluate clinicopathological characteristics of synchronous endometrial and ovarian cancers treated in our institution.Materials and Methods: The clinicopathological characteristics of 12 patients with synchronous ovarian and endometrial cancers treated at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, from July 2005 to July 2015, were reviewed retrospectively in depth from hospital database. The WHO committee classification was used for the histologic determination and staged based on International Federation of Gynaecology and Obstetrics (FIGO) staging. Results: The median age at the time of diagnosis was 50 years (range 23–66 years). The incidence of synchronous primary endometrial and ovarian cancers was 2.01% in patients with endometrial cancer. A total of seven patients were menopausal (58%) and eight patients were nulliparous (66%); the median body mass index (BMI) was 29 kg/m2 (range, 20–38). Abnormal uterine bleeding was the most common presenting symptom. According to FIGO stage, 10 cases of endometrial were Stage I/II (84%) and two cases were Stage III (16%). Of the ovarian cancers, nine cases were Stage I/II (83.3%) and two cases were Stage III (16.7%). Endometrial cancer was the main pathological type in uterine carcinoma (86%) followed by serous carcinoma (14%), and similarly, for ovarian cancer, endometrial was the most common pathology (67%) followed by serous/clear cell (16%) and mucinous (16.7%). Most endometrial and ovarian primaries in our series were Grade I and II tumours, 83% and 66%, respectively. 8 patients (66%) had similar histology in both primaries. All patients underwent surgical intervention. Only one patient did not receive any post-operative adjuvant therapy. 10 patients received platinum-based adjuvant chemotherapy and six patients received adjuvant radiotherapy. Conclusion: Synchronous primary endometrial and ovarian cancers are infrequent and distinct set of patients. Abnormal per vaginal bleed was the most common symptom which helped in early detection. Majority of the patients belong to concordant endometrial histology, low grade, had younger age and high BMI. Treatment should be tailored to the stage, histology and grade of the individual tumours. Key words: Endometrial cancer, ovarian cancer, synchronous tumours

scholarly journals Endometriosis and ovarian cancer risk

2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Javier de la Torre Fernández de Vega ◽  
Jose Luis Sánchez-Iglesias ◽  
Assumpt Perez-Benavente ◽  
Antonio Gil-Moreno ◽  
Rasheda Begum Dina ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clear Cell ◽  
Molecular Genetic ◽  
Cell Types ◽  
Ovarian Cancer Risk ◽  
New Paradigm ◽  
Ovarian Carcinomas ◽  
Genetic Studies ◽  
Ovarian Carcinogenesis ◽  
Increased Risk

Epithelial ovarian cancer presents different histological subtypes, mainly serous, mucinous, endometriod, clear cell, mixed and undifferentiated cell. Molecular genetic studies have led to a new paradigm based on a dualistic model of ovarian carcinogenesis. There is a causal association between endometriosis and specific types of ovarian carcinomas, but the magnitude of the risk is low and endometriosis is not considered a premalignant lesion. Among the endometriosis-associated ovarian tumors adenocarcinoma is the most common (Endometrioid and clear cell) (70%), sarcoma is the second most common malignancy (12%) and rare cell types 6%. The gynecologist should pay special attention to identify patients with endometriosis who may be at an increased risk for ovarian cancer.

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