Epigenetic profile of endometrial proliferation in the different morphotypes of endometrial hyperplasia

Authors

DOI:

https://doi.org/10.18370/2309-4117.2021.57.68-78

Keywords:

epigenetic profiles, endometrial hyperplasia without atypia, endometrial hyperplasia with atypia, estradiol receptor expression, progesterone receptor expression, cyclin D1, nuclear antigen Кі-67, E-cadherin, β-catenin

Abstract

Research aim: to investigate the proliferative status of endometrium in the different morphotypes of endometrial hyperplasia based upon the identification of key molecular markers of the cell cycle.
Materials and methods. Endometrial samples taken from 137 women were investigated: 40 – normal endometrium (NE), 61 – non-atypical endometrial hyperplasia (ЕH), 36 – atypical hyperplasia (AHE). Expression of gene cyclin D1, nuclear antigen Кі-67, glycoproteins Е-cadherin and β-catenin, estradiol receptors (ER) and progesterone receptors (PGR) were investigated.
Results. ER expression of NE was high in the proliferative phase and decreased significantly in the secretory phase. PGR expression was high in both phases. ER expression of EH in glandular (180 ± 8.3) and in stromal cells (170.5 ± 4.1) exceed the indicators of the secretory phase. PGR expression in the stromal cells of EH (197.5 ± 9.3) exceed significantly indicators of NE. ER and PGR expression significantly and reliably decreased if there was AHE. ER expression of glandular cells was 2.6 times lower (74.6 ± 3.9) compere to proliferative NE (p <0.05) and 2.4 times lower to EH (р <0.05). ER of stromal AHE cells dropped to 30.3 ± 2.8, which was 5.5–5.6 times lower than in the proliferative NE and EH (p <0.002). PGR expression was 2.5–2.7 times lower (71.1 ± 2.3) in AHE glands than in NE and 2.8 times lower than in EH (p <0.05). Gene cyclin D1 expression was reliably increased in AHE cells compere to NE and EH. Protein Кі-67 expression in the glandular cells of EH was 2.6 times lower (p <0.05) and in AHE 2.9 times lower (p <0.05) than NE proliferative phase. We discovered strong direction to decreasing Е-cadherin expression in EH and it was lowest for AHE. Opposite direction was expression of β-catenin. The highest numbers of positive samples were observed in AHE and it was 100%. The highest numbers of negative β-catenin samples were in the NE cells (32,5–35%).
Conclusion. The epigenetic profile investigation of endometrial hyperplasia will be useful for future development of carcinogenesis risk stratification, identifying patients with high risk of endometrial cancer and also for choosing the optimal way to influence the pathological process in the endometrium.

Author Biographies

O.L. Gromova, O.O. Bogomolets National Medical University

PhD, assistant, Obstetrics and Gynecology Department of Postgraduate Education

V.O. Potapov, SI “Dnipropetrovsk Medical Academy of the MoH of Ukraine”

MD, professor, head of the Department of Obstetrics and Gynecology

D.A. Khaskhachykh, SI “Dnipropetrovsk Medical Academy of the MoH of Ukraine”

PhD, associate professor, Department of Obstetrics and Gynecology

O.P. Finkova, Dnipro City Clinical Hospital № 9

General director

O.V. Gaponova, SI “Dnipropetrovsk Medical Academy of the MoH of Ukraine”

Assistant, Department of Obstetrics and Gynecology

G.O. Kukina, SI “Dnipropetrovsk Medical Academy of the MoH of Ukraine”

Graduate student, Department of Obstetrics and Gynecology

K.V. Penner, Kharkiv City Clinical Maternity Hospital No. 7

Physician

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Published

2021-03-31

Issue

Section

Tumors and pretumoral pathology