Relationship between methylation of Ras association domain family-1A and protein expression in endometriosis

Objective To analyze the methylation status and protein expression of Ras association domain family-1A (RASSF1A) in endometriosis (EMS). Methods The ectopic and corresponding eutopic endometrium tissues were collected from 45 women with EMS and normal endometrium tissues of 20 women without EMS. The methylation status of RASSF1A was examined by methylation specific PCR (MSP). Immunohistochemistry was performed to measure the level of RASSF1A in endometrium tissues. Results The RASSF1A protein expression rate in ectopic endometrium, eutopic endometrium, and normal endometrium was 37.78%(17/45), 60.00%(27/45) and 85.00%(17/20), and there was significant difference (χ2 = 13.136, P = 0.001). The frequency of aberrant methylation of RASSF1A was 55.56%(25/45), 33.33%(15/45) and 0 in ectopic endometrium , eutopic endometrium, and normal endometrium, and there was significant difference (χ2 =18.770, P = 0.000). The frequency of aberrant methylation of RASSF1A had no significant differnce throughout the menstrual cycle in ectopic endometrium and eutopic endometrium: 66.67%(14/21) vs. 45.83%(11/24), 38.10%(8/21) vs. 29.17% (7/24), P>0.05. In ectopic endometrium, the frequency of aberrant methylation of RASSF1A in Ⅲ-Ⅲ stage was significantly higher than that in Ⅰ-Ⅱ stage (χ2 = 5.940, P = 0.015). In ectopic endometrium and eutopic endometrium, the RASSF1A protein expression had negative correlation with aberrant methylation of RASSF1A (r = -0.594、-0.577, P<0.01). Conclusions Epigenetic inactivation of RASSF1A through aberrant promoter methylation may be strongly correlated with the formation and progression of EMS, and assessment of RASSF1A methylation status in eutopic endometrium may be a potentially useful biomarker to enhance the early detection of EMS. Key words: Endometriosis; Methylation; Immunohistochemistry; Ras association domain family-1A