Autophagy in Endometriosis: Beta-Catenin Suppressive Role

STUDY OBJECTIVE: To evaluate the occurrence of the autophagic process in ovarian endometriomas (OE), rectocervical endometriosis (RE), adenomyosis (A), and peritoneal endometriosis (PE) compared with eutopic endometrium. DESIGN: Prospective cohort study, Level II-1. SETTING: National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Healthcare of the Russian Federation. PATIENTS OR PARTICIPANTS: We recruited 120 patients with endometriosis and adenomyosis: 47 patients with (OE), 20 patients with (RE), 20 patients with (A), 33 patients with (PE). INTERVENTIONS: All patients had laparoscopic surgery performed in the proliferative non-menstrual phase of their menstrual cycle. Histological analysis was carried out according to a standard procedure. Immuno-histochemical analysis of ectopic and eutopic endometrium samples was carried out using the Tissue-Tek Quick-Ray kit, which allows for the preparation of paraffin blocks with a large number of tissue samples (tissue microarray). Antibodies to LAMP 1 (1:100), LC3 (1:50), bcl-2 (1:50), (Ventana, Roche) were used. MEASUREMENTS AND MAIN RESULTS: In patients with EO, RE, A and PE, we noticed a significant down-regulation of autophagy (LAMP1 and LC3 expression) and up-regulation of beta-catenin expression in ectopic endometrium compared with the eutopic endometrium of affected women (p<0.05). Our study did not demonstrate the difference in expression of tested markers among endometriosis lesions of different localizations (p>0.05). This data is consistent with our previous observation made on smaller number of patents, possibly confirming the data. CONCLUSION: We hypothesized that there is a relationship between autophagy and wnt/signaling pathway regulation, demonstrating the inverse ratio between beta-catenin and autophagy-marker expression. Based on the results in this study, we can say with increased certainty that increased beta-catenin could suppress autophagy, supporting ectopic endometrium through anoikis and other types of apoptosis. So we can suppose that target-based therapy suppressing the wnt/beta-catenin pathway can activate autophagy in endometriosis and, pending clinical studies, become a part of target-based pre-surgical, intra-operative, an post-operative endometriosis therapy.