Abstract
The discrimination of different subtypes of endometrial carcinoma (EC) is frequently problematic when using the current histomorphological classification; therefore, new markers for this differentiation are needed. Here, we examined differences in miRNA expression between well- and poorly-differentiated (grades 1 and 3) endometrioid endometrial carcinoma (EEC) and between EEC and serous endometrial carcinoma (SEC). The expression of 84 tumour-suppressor miRNAs was analysed by real-time polymerase chain reactions in 62 EC and 20 non-neoplastic endometrial specimens. The potential functions of the differentially expressed miRNAs were determined by bioinformatics analyses. The expression of let-7c-5p, miR-125b-5p, miR-23b-3p, and miR-99a-5p in grade 3 EEC was decreased compared to grade 1 EEC. To discriminate between EEC and SEC, let-7g-5p, miR-195-5p, miR-34a-5p, and miR-497-5p expression was significantly downregulated in SEC. In bioinformatic analyses, miRNAs that could discriminate grade 1 from grade 3 mainly targeted genes involved in PI3K-AKT signaling, whereas miRNAs that could discriminate EEC from SEC targeted genes involved in several signaling pathways, but mainly MAPK signaling. Taken collectively, our results indicate that the activation of certain signaling pathways can be useful in the molecular characterization of EEC and SEC.
Highlights
Endometrial carcinoma (EC) is one of the most common gynaecological malignancies and it associates with increasing mortality
75% of individuals are diagnosed with endometrial carcinoma (EC) at early stages (FIGO (International Federation of Gynecology and Obstetrics) I and II) and the 5-year overall survival rate of these individuals ranges from 74% to 91% compared to 66% and 26% for those diagnosed at late stages (FIGO III and IV) [2,3]
A set of 84 miRNAs showing tumour suppressor functions in different types of cancer was used for miRNA profiling in well- and poorly-differentiated endometrial carcinoma (EEC) and serous endometrial carcinoma (SEC)
Summary
Endometrial carcinoma (EC) is one of the most common gynaecological malignancies and it associates with increasing mortality. Type I (70–80% of all ECs) represents endometrioid endometrial carcinoma (EEC) with good or moderate differentiation, good prognosis, and hormone receptor overexpression. This type of EC develops from atypical hyperplasia, and the risk factors are endogenous oestrogens, nulliparity, and obesity. Type II (10–20% of all ECs) represents serous endometrial carcinoma (SEC) with poor differentiation, as well as other types, namely clear cell EC, high-grade EEC, and other undifferentiated/de-differentiated carcinomas with mesenchymal phenotypes. This type of EC is common in older women without hormonal or metabolic changes, and it develops from an atrophic endometrium and premalignant lesions. The classification of ECs with ambiguous morphologies is problematic
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