E.P. BRASLAVSKAYA, O.A. MELKOZEROVA, G.N. CHISTYAKOVA, YU.A. SEMENOV, A.A. MIKHELSON

 Ural Scientific Research Institute of Maternity and Child Care, Yekaterinburg

 Contact details:

Braslavskaya E.P. — obstetrician-gynecologist of the Department of Reproductive Function Preservation

Address: 1 Repin St., 620028 Yekaterinburg, Russian Federation, tel.: +7-922-213-26-91 e-mail: lenabraslavskaya1@gmail.com

 Endometriosis is characterized by an infiltrative growth, with a tendency to recurrent course in 40–50% of cases within a 5-year observation and the formation of chronic pelvic pain and infertility in women of reproductive age.

The purpose — to identify some molecular-biological mechanisms of recurrent course of deep endometriosis based on a comparative analysis of the activity of proliferative, proapoptotic and antiapoptotic signaling pathways in ectopic and eutopic endometrium.

Material and methods. The study included 113 patients of reproductive age who underwent surgical treatment of widespread forms of external genital endometriosis. The first group consisted of 32 patients of reproductive age who underwent repeated surgical treatment due to recurrence of deep endometriosis, the second group — 51 patients without recurrence of the disease one year after the primary surgery for deep endometriosis, the third group — 30 fertile patients of reproductive age without endometriosis. The patients underwent an immunohistochemical (IHC) study to determine the expression levels of steroid receptors for estrogen (ER1) and progesterone (PR), regulators of apoptosis (p53, Bcl-2, AKT, PTEN) and angiogenesis (VEGF R1) in the epithelium of the glands and the stroma of ectopic endometrium in patients with deep endometriosis depending on the recurrence status, and of etiologic endometrium in patients without endometriosis.

Results. It was found that in patients with recurrent deep endometriosis, compared to women with non-recurrent diseases, there was a significantly higher level of ER1 expression in the glands and stroma of ectopic endometrium foci. The stromal ratio of steroid reception ER/PR in the endometriosis foci was maximal in patients with recurrent deep endometriosis. A significantly lower level of expression of the p53 marker in the stroma of ectopic endometrial foci was found in patients with recurrent disease. In the stroma of the ectopic endometrium of patients with recurrent deep endometriosis, the levels of expression of the apoptosis blocker Bcl-2 were significantly higher. The levels of expression of protein kinase AKT, the anti-apoptotic signaling pathway PI3K/AKT/mTOR were significantly higher in the glands of ectopic endometrium foci in patients with recurrent deep endometriosis. In the stroma and glands of endometrioid foci, the expression of PTEN was significantly lower than in the eutopic endometrium of patients without endometriosis (p < 0.05).

Conclusion. Significant differences of the molecular-biological pattern of expression of p-53 dependent apoptosis and the anti-apoptotic signaling pathway PIK3CA/Akt/mTOR in the ectopic endometrium of patients with recurrent endometriosis, in contrast to non-recurrent forms of the disease and the eutopic endometrium of fertile women, may be one of the mechanisms of the recurrent disease.

Key words: angiogenesis, apoptosis, pain, deep infiltrative endometriosis, disease relapse, estrogen receptors.

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