PROBABILITY OF NEOPLASTIC TRANSFORMATION IN DIFFERENT TYPES OF ENDOMETRIAL HYPERPLASIA

Objective. To determine the probability of malignization of different types of endometrial hyperplasia, by using the most informative indicators of expression of the mRNA genes presumably involved in the development of hyperand neoplastic endometrial processes. Subject and methods. Clinical and laboratory examinations involving endometrial tissue sampling were made in 111 women. A study group included 58 patients with endometrial hyperplasia (31, 15, and 12 with simple, complex, and atypical hyperplasia, respectively); a comparison group consisted of 16 patients with low-grade endometrioid adenocarcinoma; a control group comprised 47 women with the morphologically unaltered endometrium in the stage of proliferation (n = 26) or secretion (n = 21). RT-PCR was used to study mRNA in 19 genes regulating the cell cycle, proliferation, apoptosis, invasion, cell receptor phenotype (PTEN, MKI67 (KI67), CCNB1, BIRC5, AURKA, MYBL2, CDKN2A (p16), NDRG1, BCL2, BAX, BAG1, CTSL2, MMP11, ESR1, PGR, CD68, PTGS2 (COX2), CYP19A1, and SCUBE2). Results. A statistical model including the expression levels in 5 genes, such as PTEN, PGR, NDRG1, CTSL2, and SCUBE2, was built to create an integral criterion for the probability of endometrioid adenocarcinoma by binary logistic regression. The area under the ROC curve was 0.984±0.16 (p < 0.0001). The application of the developed model could classify correctly 93.8% of the morphologically verified endometrioid adenocarcinoma samples; 19, 20, and 42% of the simple, complex, and atypical endometrial hyperplasia samples were referred to as an area to be at high risk for neoplastic transformation of the endometrium. Conclusion. By using the mathematical criteria, the investigators identified 5 most significant genes out of 19 ones under study. These included PTEN, PGR, NDRG1, CTSL2, and SCUBE2 and were used to propose a statistical model as a linear equation that offered a means of objectively identifying a group of patients who were presumably at higher risk of cancer. They deserve special attention, diagnostic monitoring, risk factor modifications, long-term adequate hormone therapy or surgical treatment.

endometrial hyperplasia, endometrial cancer, RT-PCR