Immunohistochemical features of eutopic and ectopic endometrium in patients with recurrent ovarian endometrioid cysts


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Abstract

Objective. To investigate the expression of proliferation and apoptosis markers (Ki-67, Bcl-2), inf lammatory factors (NF-kß p65, COX-2), adhesion factors (ß-catenin), estrogen receptor-a (ER-a) and progesterone receptor-a (PR-a) in the eutopic endometrium and ovarian endometrioid cyst (OEC) sac in patients with recurrent OEC, by using an immunohistochemical assay. Subjects and methods. The investigation enrolled 60 reproductive-aged patients with OEC treated in the Department of Operative Gynecology, V.I. Kulakov Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, in 2015-2016. According to the course of the disease during a 1.5-year follow-up after surgical treatment, the patients were divided into two groups: 1) 41 patients without recurrent OEC (a comparison group); 2) 19 patients with recurrent OEC (a study group). The investigation used histological and immunohistochemical examinations. The histological examination of the endometrium and OEC sacs was performed using a standard procedure. The immunohistochemical examination of the eutopic endometrium and OEC sac was done using the Tissue-Tek Quick-Ray kit that allows one to make paraffin blocks containing a large number of tissue samples (tissue matrices). The investigation used antibodies against Ki-67 (clone 30-9, VENTANA), Bcl-2 (clone 124, VENTANA), NF-kß p65 (clone p65, Spring Bioscience Corp.), COX-2 (clone СХ-294, Agilent), ß-catenin (clone 14, VENTANA), ER-a (clone SP1, VENTAN), and PR-a (clone 1E2, VENTANA). The specimens were prepared according to the standard protocol using a Ventana Ultra immunohistostainer. Positive and negative controls were used to correctly make immunohistochemical assays. Statistical analysis was carried out using the applied statistical analysis software (Statistica 10.0, Microsoft Excel). Results. The immunohistochemical examination showed that the ectopic endometrium (OEC sac) was characterized by a change in the expression of ER-a, PR-a, Ki-67, Bcl-2, NF-kß p65, COX-2, and ß-catenin, which are the factors involved in the pathogenesis of endometriosis. The patients with recurrent OEC had an increased PR-a expression in the epithelial component of the OEC sac (p = 0.0277), a reduced Ki-67 expression in it (p = 0.044), a reduced NF-kß p65 and COX-2 expression in the stromal component of the OEC sac (p = 0.0082; p = 0.00245, respectively) and an increased ß-catenin expression in it (p = 0.017). The immunohistochemical examination revealed that the patients with recurrent OEC showed increases in the expression of PR-a in the epithelial component of the eutopic endometrium in the secretory phase (p = 0.0253) and in that of NF-kß p65 in the stromal component of the eutopic endometrium in the proliferative phase (p = 0.0278). Conclusion. The immunohistochemical examination of the expression of PR-a, Ki-67, NF-kß p65, COX-2, and ß-catenin in the OEC sac and that of PR-a and NF-kß p65 in the eutopic endometrium can assist in identifying patients at high risk for recurrent OEC immediately after surgical treatment. Further investigations of these factors will be able to study the molecular mechanisms underlying the pathogenesis of recurrent OEC, which will affect these mechanisms to eliminate the fundamental causes of recurrent endometriosis.

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About the authors

Ekaterina Yurievna Pshenichnyuk

National Medical Research Center of Obstetrics, Gynecology, and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia

Email: best-kauty@mail.ru
PhD-student, Department of Surgical Gynecology

Alexandra Vyacheslavovna Asaturova

National Medical Research Center of Obstetrics, Gynecology, and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia

Email: a_asaturova@oparina4.ru
PhD, senior scientific researcher of pathology department

Leila Vladimirovna Adamyan

National Medical Research Center of Obstetrics, Gynecology, and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia

MD, professor, academician of RAS; deputy director on science, head of department of operative gynecology

Nikon Vladimirovich Zaitsev

National Medical Research Center of Obstetrics, Gynecology, and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia

pathologist of pathology department

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