MMAC tumor supressor gene expression in ovarian endometriosis and ovarian adenocarcinoma

Objective: The aim of this study was to investigate the role of MMAC1 protein in the relationship between ovarian endometriosis and clear cell and endometrioid-type ovarian adenocarcinomas.

Methods: A total of 63 subjects who underwent surgery for a pelvic tumoral mass, 30 of whom were diagnosed with grade 1 to 3 ovarian adenocarcinoma and 33 of whom were diagnosed with grade 1 to 4 endometriosis during histopathological examination were included in this study. The mean age for subjects with ovarian endometrioid type adenocarcinoma was 51.8 +/- 12.4, whereas the mean age for subjects with ovarian clear cell type adenocarcinoma was 59.5 +/- 13.7. Ovarian carcinomas were graded in accordance with the FIGO 1989 grading system. The mean age for subjects with endometriosis was 37 +/- 11.9. New sections were obtained from paraffin blocks in the archives of Ege University, School of Medicine, Department of Pathology onto lysinated slides and immunohistochemical staining by using mouse monoclonal antibody (MMAC1, 28H6 clone, Novocastra, UK) as MMAC antibody was applied in order to determine MMAC1 protein. Brown staining on the nucleus was considered as positive immunoreactivity. Immunoreactive staining was evaluated as percentage staining over the whole preparative.

Results: Of the 63 subjects included in the immunohistochemical study, ovarian endometrioid adenocarcinoma was identified in 18 subjects, while 12 subjects were diagnosed with ovarian clear cell adenocarcinoma and 33 subjects with ovarian endometriosis. No significant relationships were observed between age and MMAC immune staining in the ovarian endometrioid adenocarcinoma (r = -0.41, p = 0.08) and ovarian endometriosis (r = 0.12, p = 0.50) groups, whereas a significant relationship was observed in the ovarian clear cell adenocarcinoma group (r = 0.631, p = 0.02). No significant relationships were observed between CA125 levels and MMAC immune staining in the ovarian endometrioide adenocarcinoma (r = 0.056, p = 0.82), ovarian endometriosis (r = 0.21, p = 0.36) and ovarian clear cell adenocarcinoma (r = 0.363, p = 0.24) groups. No correlations were observed between endometriosis stages and the MMAC immune staining (r = -0.17, p = 0.92). There was no correlation between mean diameter of endometrioma and MMAC immune staining (r = -0.230, p = 198). Mean endometrioma diameter was 5.7 +/- 3.5 (1-15.5). No correlations were detected between MMAC immune staining and ovarian endometrioide adenocarcinoma or ovarian clear cell adenocarcinoma stage (r = -0.22, p = 0.37; r = 0.44, p = 0.14, respectively). No significant relationships with respect to MMAC immune staining were detected between the endometriosis and ovarian clear cell adenocarcinoma groups (p = 0.05) and between the ovarian clear cell adenocarcinoma and ovarian endometrioid adenocarcinoma groups (p = 0.27). A significant relationship with respect to MMAC immune staining was observed between ovarian endometrioide adenocarcinoma and endometriosis groups (p = 0.001).

Conclusion: Immunohistochemical determination of MMAC defective protein expressions could be considered for utilization as a new, simple and useful technique in determination of endometriosis patients with increased risk of malignant transformation, patients where early surgical treatment would be necessary and patients that should be subjected to follow-up controls with a higher frequency.

Endometriosis; MMAC protein; Ovarian adenocarcinoma

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