Fang Ren1, Dan-bo Wang, Tong Li. 1. Department of Obstetrics and Gynecology, China Medical University, Shenyang, China.
Abstract
OBJECTIVE: To investigate epigenetic inactivation of SPOCK2 gene in the malignant transformation of ovarian endometriosis (EM) by comparing the methylation status and protein expression of SPOCK2 gene in the malignant tissues, ectopic endometria and the eutopic endometria of endometriosis. METHODS: From Jan. 2005 to Jan. 2011, 22 paraffin-embedded specimens diagnosed as malignant transformation of ovarian endometriosis (EAOC) including 11 cases with ovarian endometrioid carcinoma, 8 cases with clear cell carcinoma, 2 cases with serous cystadenocarcinoma and 1 case with mucous cystoadenocarcinoma matched with 22 cases with ovarian endometriosis and 16 cases with normal endometrium form cervical intraepithelial neoplasia(CIN) patients as controls in Department of Obstetrics and Gynecology of Shengjing Hospital. Twenty-two malignant tissues, 15 ectopic endometria and 10 eutopic endometria were captured by microdissection in EAOC group; 22 ectopic endometria and 17 eutopic endometria were captured in EM group; 22 endometrium were captured in the NE group. The methylation statue of SPOCK2 was determined by combined bisulfite restriction analysis, and the protein expression of SPOCK2 was evaluated by immunohistochemistry. RESULTS: (1) Methylation of SPOCK2: in the EAOC group, the frequency of SPOCK2 hypermethylation in malignant tissue was 45% (10/22), which was significantly higher than 1/15 in the ectopic endometrium (P < 0.05). There was no statistical difference of the frequency of SPOCK2 hypermethylation in ectopic endometrium in the EAOC group (1/15) and EM group (5%, 1/22) (P > 0.05). (2) SPOCK2 protein: the loss rate of SPOCK2 was 44% (11/22) in malignant tissue in EAOC group, which were significantly higher than 2/15 of in ectopic endometrium of EAOC (P < 0.05). However, there was no remarkable difference in loss rate of SPOCK2 protein between ectopic endeometrium of EAOC and endometrium of EM [2/15 vs. 5% (1/22), P > 0.05]. No significantly difference in loss rate of SPOCK2 in eutopic endometrium was observed among three groups (P > 0.05). (3) The abnormal methylation of SPOCK2 could lead to loss expression of protein (P < 0.05). CONCLUSION: Epigenetic inactivation of SPOCK2 gene is involved in the malignant transformation of ovarian endometriosis.
OBJECTIVE: To investigate epigenetic inactivation of SPOCK2 gene in the malignant transformation of ovarian endometriosis (EM) by comparing the methylation status and protein expression of SPOCK2 gene in the malignant tissues, ectopic endometria and the eutopic endometria of endometriosis. METHODS: From Jan. 2005 to Jan. 2011, 22 paraffin-embedded specimens diagnosed as malignant transformation of ovarian endometriosis (EAOC) including 11 cases with ovarian endometrioid carcinoma, 8 cases with clear cell carcinoma, 2 cases with serous cystadenocarcinoma and 1 case with mucous cystoadenocarcinoma matched with 22 cases with ovarian endometriosis and 16 cases with normal endometrium form cervical intraepithelial neoplasia(CIN) patients as controls in Department of Obstetrics and Gynecology of Shengjing Hospital. Twenty-two malignant tissues, 15 ectopic endometria and 10 eutopic endometria were captured by microdissection in EAOC group; 22 ectopic endometria and 17 eutopic endometria were captured in EM group; 22 endometrium were captured in the NE group. The methylation statue of SPOCK2 was determined by combined bisulfite restriction analysis, and the protein expression of SPOCK2 was evaluated by immunohistochemistry. RESULTS: (1) Methylation of SPOCK2: in the EAOC group, the frequency of SPOCK2 hypermethylation in malignant tissue was 45% (10/22), which was significantly higher than 1/15 in the ectopic endometrium (P < 0.05). There was no statistical difference of the frequency of SPOCK2 hypermethylation in ectopic endometrium in the EAOC group (1/15) and EM group (5%, 1/22) (P > 0.05). (2) SPOCK2 protein: the loss rate of SPOCK2 was 44% (11/22) in malignant tissue in EAOC group, which were significantly higher than 2/15 of in ectopic endometrium of EAOC (P < 0.05). However, there was no remarkable difference in loss rate of SPOCK2 protein between ectopic endeometrium of EAOC and endometrium of EM [2/15 vs. 5% (1/22), P > 0.05]. No significantly difference in loss rate of SPOCK2 in eutopic endometrium was observed among three groups (P > 0.05). (3) The abnormal methylation of SPOCK2 could lead to loss expression of protein (P < 0.05). CONCLUSION: Epigenetic inactivation of SPOCK2 gene is involved in the malignant transformation of ovarian endometriosis.