Molecular Features of Endometrial Cancer: Entering the Era of Precision Medicine. Review.

Abstract

Endometrial cancer is the third most common cancer in women in Russia, with a prevalence of 191.6 cases per 100,000 persons in 2021. This disease is extremely rare before the age of 40, it rarely occurs from 40 to 50, and gradually increases with age, peaking at the age of 63. Generally, endometrial cancer is diagnosed on early stages, with an overall 5-year survival rate of over 95 %. However, survival declines significantly with regional or distant metastasis, amounting to 68 % and 17 %, respectively. Historically, endometrial carcinoma has been classified into two main clinicopathologic types: endometrioid adenocarcinomas and non-endometrioid carcinomas such as serous, clear cell, undifferentiated carcinomas, and carcinosarcomas. However, The Cancer Genome Atlas (TCGA) has expanded our understanding of the molecular landscape of endometrial cancer by presenting four molecular subtypes: tumors with mutations in the POLE gene, microsatellite instable carcinomas, tumors with mutations in the TP53 gene, and carcinomas of the non-specific molecular subtype. The integration of molecular classification into clinical practice has changed patient risk grouping, which, in turn, affected the choice of adjuvant therapy. Patient rehabilitating and ensuring a high quality of life is a complex issue that requires striking a balance between reducing the risk of relapse and preventing side effects associated with unjustifiable escalation of treatment. The review provides the data on endometrial cancer molecular subtypes, surrogate markers, and determination methods. The predictive value of molecular classification has been discussed, along with its potential use in further clinical trial designs.