EXPRESSION OF APOPTOSIS-REGULATORY GENES IN DIFFERENT ENDOMETRIAL HYPERPLASIA TYPES AND ENDOMETRIOID CARCINOMA


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Abstract

Objective: to determine the clinical value of expression of mRNA genes involved in the processes of apoptosis and the potent tumor growth suppressor gene PTNE in different endometrial hyperplasia types and endometrioid carcinoma. Subjects and methods. Clinical and laboratory examinations and endometrial tissue sampling were made in 133 women. A study group included 64 patients with endometrial hyperplasia (31, 18, and 15 with simple, complex, and atypical hyperplasia, respectively); a comparison group consisted of 22 patients with endometrioid carcinoma; a control group comprised 47 women with morphologically unaltered endometrium in the stage of proliferation (n=26) or secretion (n=21). RT-PCR was used to study the mRNA expression of apoptotic genes: the inhibitors — BCL2, BAG1, BIRC5 and the inductors — BAX, NDRG1. PTEN gene expression was determined by two independent methods (RT-PCR and immunohistochemical assay). Results. RT-PCR failed to reveal significant differences in the expression of apoptosis-regulatory genes between different types of endometrial hyperplasia. There was a significant reduction in the mRNA expression of the NDRG1 and PTEN genes and in the NDRG1/BIRC5 index in the tissue of endometrioid carcinoma versus the hyperplastic and morphologically altered endometrium (p<0.05). Immunohistochemical evidence supported the obtained pattern; PTEN expression loss was established in 45.4% of the endometrial tissue samples in endometrioid carcinoma. Conclusion. The findings suggest that programmed cell death seems to be responsible for the development of endometrioid carcinoma. The decrease in the mRNA expression of the NDRG1 and PTEN genes and in the NDRG1/BIRC5 index may be supposedly considered as molecular genetic predictors of a risk for endometrial cancer transformation.

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About the authors

G. E CHERNUKHA

Academician V. I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

Email: g_chernukha@oparina4.ru
Moscow,Russia

M. R DUMANOVSKAYA

Academician V. I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

Email: m_dumanovskaya@oparina4.ru
Moscow,Russia

O. V BURMENSKAYA

Academician V. I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

Email: o_ bourmenska@mail.ru
Moscow,Russia

E. S SHUBINA

Academician V. I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

Email: jekaterina.shubina@gmail.com
Moscow,Russia

E. A KOGAN

Academician V. I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

Email: e_kogan@oparina4.ru
Moscow,Russia

D. YU TROFIMOV

Academician V. I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health and Social Development of Russia

Email: d_trofimov@oparina4.ru
Moscow,Russia

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