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 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.

scholarly journals Ultrasound, macroscopic and histological features of serous epithelial ovarian carcinomas

2020 ◽  
pp. ijgc-2020-001473
Author(s):  
Paola Romeo ◽  
Damiano Arciuolo ◽  
Maria Cristina Moruzzi ◽  
Francesca Moro
Keyword(s):  
Ovarian Carcinoma ◽  
Low Grade ◽  
High Grade ◽  
Ovarian Carcinomas ◽  
Histological Features ◽  
Serous Ovarian Carcinoma ◽  
Epithelial Ovarian Carcinomas

We present a video showing two cases of serous epithelial ovarian carcinomas. The first video shows clinical, ultrasound, macroscopic, and histological features of a patient with high grade serous ovarian carcinoma. The second video presents clinical, ultrasound, macroscopic, and histological features of a patient with low grade serous ovarian carcinoma.

Survival Rates for International Federation of Gynecology and Obstetrics Stage III Ovarian Carcinoma by Cell Type: A Study of 262 Unselected Patients With Uniform Pathologic Review

2012 ◽  
Vol 22 (3) ◽  
pp. 367-371 ◽  
Author(s):  
Jeffrey D. Seidman ◽  
Anna Yemelyanova ◽  
Jonathan A. Cosin ◽  
Anthony Smith ◽  
Robert J. Kurman
Keyword(s):  
Ovarian Cancer ◽  
International Federation ◽  
Stage Iii ◽  
Serous Carcinoma ◽  
Published Data ◽  
Low Grade ◽  
High Grade ◽  
Cell Type ◽  
Ovarian Carcinomas ◽  
Gynecology And Obstetrics

ObjectivePublished data are conflicting on the influence of cell type on prognosis in ovarian cancer. The recent separation of low-grade serous carcinoma as a distinctive cell type of ovarian cancer with an indolent behavior, in retrospect, suggests that survival in studies that have not separated this group may be inaccurate.MethodsAn unselected series of 262 International Federation of Gynecology and Obstetrics stage III ovarian carcinomas was studied. Diagnostic classification of each tumor was made with particular attention to recent refinements in cell-type classification. Survival curves were constructed according to Kaplan-Meier and compared with the log-rank test.ResultsThe 5-year survival for 207 high-grade serous carcinomas was 40%, as compared with 71% for 18 patients with low-grade serous carcinoma (P = 0.0113). Low-grade serous carcinoma was significantly more likely to be optimally debulked (P = 0.0039) and significantly less likely to be substage IIIC (P < 0.0001). The survival for carcinosarcoma was significantly inferior to all serous carcinomas (P = 0.0322). The significance of this latter comparison was lost when carcinosarcomas were compared with only high-grade serous carcinoma (P > 0.05).ConclusionsLow-grade serous carcinoma has a significantly better prognosis than high-grade serous carcinoma and also differs with regard to substage distribution and proportion of patients optimally debulked. Because of its excellent prognosis, failure to separate low-grade serous carcinomas, notwithstanding its infrequent occurrence, can change the results of survival analyses that do not make this separation.

scholarly journals The Evolution of Ovarian Carcinoma Subclassification

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 416
Author(s):  
Martin Köbel ◽  
Eun Young Kang
Keyword(s):  
Ovarian Carcinoma ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Expression Profiles ◽  
Model Systems ◽  
Serous Carcinoma ◽  
Molecular Profile ◽  
Low Grade ◽  
Ovarian Carcinomas ◽  
Immunohistochemical Markers

The phenotypically informed histotype classification remains the mainstay of ovarian carcinoma subclassification. Histotypes of ovarian epithelial neoplasms have evolved with each edition of the WHO Classification of Female Genital Tumours. The current fifth edition (2020) lists five principal histotypes: high-grade serous carcinoma (HGSC), low-grade serous carcinoma (LGSC), mucinous carcinoma (MC), endometrioid carcinoma (EC) and clear cell carcinoma (CCC). Since histotypes arise from different cells of origin, cell lineage-specific diagnostic immunohistochemical markers and histotype-specific oncogenic alterations can confirm the morphological diagnosis. A four-marker immunohistochemical panel (WT1/p53/napsin A/PR) can distinguish the five principal histotypes with high accuracy, and additional immunohistochemical markers can be used depending on the diagnostic considerations. Histotypes are further stratified into molecular subtypes and assessed with predictive biomarker tests. HGSCs have recently been subclassified based on mechanisms of chromosomal instability, mRNA expression profiles or individual candidate biomarkers. ECs are composed of the same molecular subtypes (POLE-mutated/mismatch repair-deficient/no specific molecular profile/p53-abnormal) with the same prognostic stratification as their endometrial counterparts. Although methylation analyses and gene expression and sequencing showed at least two clusters, the molecular subtypes of CCCs remain largely elusive to date. Mutational and immunohistochemical data on LGSC have suggested five molecular subtypes with prognostic differences. While our understanding of the molecular composition of ovarian carcinomas has significantly advanced and continues to evolve, the need for treatment options suitable for these alterations is becoming more obvious. Further preclinical studies using histotype-defined and molecular subtype-characterized model systems are needed to expand the therapeutic spectrum for women diagnosed with ovarian carcinomas.

scholarly journals Immunohistochemical Biomarkers as a Surrogate of Molecular Analysis in Ovarian Carcinomas: A Review of the Literature

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 199 ◽  
Author(s):  
Giacomo Santandrea ◽  
Simonetta Piana ◽  
Riccardo Valli ◽  
Magda Zanelli ◽  
Elisa Gasparini ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Molecular Analysis ◽  
Immunohistochemical Analysis ◽  
Cost Effective ◽  
Mucinous Carcinoma ◽  
Serous Carcinoma ◽  
Malignant Neoplasms ◽  
Low Grade ◽  
Ovarian Carcinomas ◽  
Novel Target

The term “ovarian carcinoma” encompasses at least five different malignant neoplasms: high-grade serous carcinoma, low-grade serous carcinoma, endometrioid carcinoma, mucinous carcinoma, and clear cell carcinoma. These five histotypes demonstrated distinctive histological, molecular, and clinical features. The rise of novel target therapies and of a tailored oncological approach has demanded an integrated multidisciplinary approach in the setting of ovarian carcinoma. The need to implement a molecular-based classification in the worldwide diagnostic and therapeutic setting of ovarian cancer demanded a search for easy-to-use and cost-effective molecular-surrogate biomarkers, relying particularly on immunohistochemical analysis. The present review focuses on the role of immunohistochemistry as a surrogate of molecular analysis in the everyday diagnostic approach to ovarian carcinomas.

Different effects of bronchoscopic interventions on children and adults with tracheobronchial mucoepidermoid carcinoma

2021 ◽  
pp. 030089162199589
Author(s):  
Zhang Jieli ◽  
Zhou Yunzhi ◽  
Zhang Nan ◽  
Zou Heng ◽  
Wang Hongwu ◽  
...  
Keyword(s):  
Mucoepidermoid Carcinoma ◽  
Argon Plasma Coagulation ◽  
Survival Rates ◽  
Argon Plasma ◽  
Rigid Bronchoscopy ◽  
Low Grade ◽  
High Grade ◽  
Adult Group ◽  
Histologic Grading ◽  
Comprehensive Therapy

Aims: To investigate the efficacy and safety of minimally invasive bronchoscopic interventions for patients with tracheobronchial mucoepidermoid carcinoma (MEC). Methods: Patients with tracheobronchial MEC were included in this retrospective study, and the clinical features, histologic grading, treatments, and cumulative survival rates were calculated. Patients were categorized into child (n = 16) and adult (n = 19) group according to their ages. Histologic grading, treatments, and survival status were compared between the two groups. Results: In pathology, high-grade MEC counts for 6.77% and 42.10% in the child and adult group, respectively. As tumor growth pattern was concerned, 93.33% and 21.05% tumors in the child and adult group present intratracheal type. Multiple bronchoscopic interventions were conducted, including rigid bronchoscopy, argon plasma coagulation (APC), dioxide carbon cryotherapy, and electric loop. Tumors could be removed by multiple bronchoscopic interventions. Bronchoscopy-associated complications were rare, including an oral mucosa injury and a glottis edema. In the child group, one patient underwent left upper lung lobectomy. In the adult group, lobectomy and/or chemotherapy and/or radiotherapy were conducted in seven patients. The 5-year survival rate was 100% and 68.90% in the child and the adult group, respectively. Conclusions: Almost all children have low-grade and intratracheal MEC; 2/5 adults have invasive high-grade MEC. Multiple bronchoscopic interventions are effective in erasing low-grade intratracheal MEC without severe complications. For high-grade invasive MEC, aggressive and comprehensive therapy should be considered.

scholarly journals Trace Amine-Associated Receptor 1 (TAAR1) Is a Positive Prognosticator for Epithelial Ovarian Cancer

2021 ◽  
Vol 22 (16) ◽  
pp. 8479
Author(s):  
Tilman L. R. Vogelsang ◽  
Aurelia Vattai ◽  
Elisa Schmoeckel ◽  
Till Kaltofen ◽  
Anca Chelariu-Raicu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Epithelial Ovarian Cancer ◽  
Tnm Classification ◽  
Rank Correlation ◽  
University Hospital ◽  
Cancer Tissue ◽  
Low Grade ◽  
High Grade ◽  
Trace Amine

Trace amine-associated receptor 1 (TAAR1) is a Gαs- protein coupled receptor that plays an important role in the regulation of the immune system and neurotransmission in the CNS. In ovarian cancer cell lines, stimulation of TAAR1 via 3-iodothyronamine (T1AM) reduces cell viability and induces cell death and DNA damage. Aim of this study was to evaluate the prognostic value of TAAR1 on overall survival of ovarian carcinoma patients and the correlation of TAAR1 expression with clinical parameters. Ovarian cancer tissue of n = 156 patients who were diagnosed with epithelial ovarian cancer (serous, n = 110 (high-grade, n = 80; low-grade, n = 24; unknown, n = 6); clear cell, n = 12; endometrioid, n = 21; mucinous, n = 13), and who underwent surgery at the Department of Obstetrics and Gynecology, University Hospital of the Ludwig-Maximilians University Munich, Germany between 1990 and 2002, were analyzed. The tissue was stained immunohistochemically with anti-TAAR1 and evaluated with the semiquantitative immunoreactive score (IRS). TAAR1 expression was correlated with grading, FIGO and TNM-classification, and analyzed via the Spearman’s rank correlation coefficient. Further statistical analysis was obtained using nonparametric Kruskal-Wallis rank-sum test and Mann-Whitney-U-test. This study shows that high TAAR1 expression is a positive prognosticator for overall survival in ovarian cancer patients and is significantly enhanced in low-grade serous carcinomas compared to high-grade serous carcinomas. The influence of TAAR1 as a positive prognosticator on overall survival indicates a potential prognostic relevance of signal transduction of thyroid hormone derivatives in epithelial ovarian cancer. Further studies are required to evaluate TAAR1 and its role in the development of ovarian cancer.

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.

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