Molecular characteristics of endometrial cancer: entering the era of precision medicine

Abstract

Endometrial cancer ranks third among cancers affecting women in Ukraine, with a tendency to incidence rate increase every year. The disease is extremely rare in women under 40, and uncommon between 40 and 50, but thereafter, as age increases, the incidence curve rises sharply, peaking at around 63 years of age. As a rule, the disease is diagnosed at an early stage, with an overall 5-year survival rate exceeding 95%. However, this rate drops significantly in cases of regional or distant spread, standing at 68% and 17% respectively. Historically, endometrial carcinoma was classified into two main clinical-pathological types. The first type comprised endometrioid adenocarcinomas, whilst the second included nonendometrioid tumours (serous, clear cell, undifferentiated carcinomas and carcinosarcomas). However, the work carried out in compiling The Cancer Genome Atlas (TCGA) has transformed our understanding of the molecular landscape of endometrial cancer, identifying not two but four molecular subtypes: tumours with mutations in the POLE gene, microsatellite-unstable carcinomas, tumours with mutations in the TP53 gene, and carcinomas of an unspecified molecular subtype. The integration of molecular classification into clinical practice has altered the stratification of patients into risk groups, which, in turn, has influenced the choice of adjuvant therapy. The rehabilitation of patients and ensuring a high quality of life is a very complex task, and to address it, an appropriate balance is required between reducing the risk of recurrence and preventing side effects associated with unjustified escalation of treatment. This review presents information on the molecular subtypes of endometrial cancer, surrogate markers for each molecular subtype, and methods for their determination. The prognostic significance of molecular classification is discussed, as well as the prospects for its use in the design of future studies.