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Abstract
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.
References
Имянитов И.Н., Хансон К.П. Молекулярная онкология: клинические аспекты. - СПб.: СПбМАПО, 2007. - 211 с.
Покатаев И.А, Тюляндин С.А. Общие принципы лекарственной терапии опухолей женской половой сферы // http:ovariancancer.ru/specialistam/generalprinciplesofchemo.htm
Banerjee S., Kaye S.B. New strategies in the treatment of ovarian cancer: current clinical perspectives and future potential // Clin. Cancer Res. - 2013. - Vol. 19 (5). - P. 961-968. DOI: 10.1158/1078-0432.CCR-12-2243
Biotargets of Cancer in Current Clinical Practice / Mauro Bologna. Springer Science & Business Media, 2012. - P. 563.
Bonome T., Levine D.A., Shih J. et al. A gene signature predicting for survival in suboptimally debulked patients with ovarian cancer // Cancer Res. - 2008. - Vol. 68(13). - P. 5478-5486.
Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma // Nature. - 2011. - Vol. 474 (7353). - P. 609-615.
Chen G.M., Kannan L., Geistlinger L. et al. Consensus on Molecular subtypes of ovarian Cancer // bioRxiv. - 2017. - abstr. 162685. - DOI: 10.1101/162685
Gourley C., McCavigan A., Perren T. et al. Molecular subgroup of high-grade serous ovarian cancer (HGSOC) as a predictor of outcome following bevacizumab // J. Clin. Oncol. - 2014. - Vol. 32(15). - suppl.5502. - DOI: 10.1200/jco.2014.32.15_suppl.5502
Helland A., Anglesio M.S., George J. et al. Deregulation of MYCN, LIN28B and LET7 in a molecular subtype of aggressive high-grade serous ovarian cancers // PLoS One. - 2011. - Vol. 6(4). - 10.1371/journal. pone.0018064. DOI: 10.1371/journal.pone.0018064
Kommoss S., Winterhoff B., Oberg A.L. et al. Bevacizumab May Differentially Improve Ovarian Cancer Outcome in Patients with Proliferative and Mesenchymal Molecular Subtypes // Clin. Cancer Res. - 2017. - Vol. 23(14). - P. 3794-3801. - DOI: 10.1158/1078-0432.CCR-16-2196
Konecny G.E., Wang C., Hamidi H. et al. Prognostic and therapeutic relevance of molecular subtypes in high-grade serous ovarian cancer// J. Natl. Cancer Inst. - 2014. - Vol. 106(10). -. DOI: 10.1093/jnci/dju249
Kurman R.J., Shih le M. Molecular pathogenesis and extra-ovarian origin of epithelial ovarian cancer-shifting the paradigm //Hum. Pathol. - 2011. - Vol. 42. - P. 918-931.
Lohr J.G., stojanov P., Carter s.L. et al. Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy // Cancer Cell. - 2014. - Vol. 25(1). - P. 91-101
Michiels S., Rotolo F. Evaluation of clinical utility and validation of gene signatures in clinical trials. In Matsui S., Buyse M., Simon R. (eds). Design and Analysis of Clinical Trials for Predictive Medicine. Boca Raton, Florida: CRC Press, 2015. - P. 187-203.
Tothill R.W., Tinker A.V., George J. et al. Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome // Clin Cancer Res. - 2008. - Vol. 14. - P. 5198-5208. - CCR-08-0196. DOI: 10.1158/1078-0432
Verhaak R.G., Tamayo P., Yang J. et al. Cancer Genome Atlas Research Network: Prognostically relevant gene sig natures of highgrade serous ovarian carcinoma // J. Clin. Invest. - 2013. - Vol. 123. - P. 517-525.
Way G.P., Rudd J., Wang C. et al. Comprehensive Cross-Population Analysis of High-Grade Serous Ovarian Cancer Supports No More Than Three Subtypes. G3 (Bethesda). - 2016. - Vol. 6(12). - P. 4097-4103. - DOI: 10.1534/g3.116.033514
Winterhoff B., Kommoss s., oberg A.L. et al. Bevacizumab may differentially improve survival for patients with the proliferative and mesenchymal molecular subtype of ovarian cancer // Journal of Clinical oncology. - 2014. - Vol. 32(15). - suppl. - P. 5509-5509. - DOI: 10.1158/1078-0432.CCR-16-2196
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