Expression of cell cycle regulatory proteins in ovaries prophylactically removed from Jewish Ashkenazi BRCA1 and BRCA2 mutation carriers: Correlation with histopathology

Objectives. Prophylactic oophorectomy in Ashkenazi Jewish women with BRCA mutations represents a unique opportunity to search for premalignant changes in ovaries. Reports on the presence of dysplastic lesions in these ovaries are contradictory. Our aim was to study the expression of cell cycle regulatory proteins-p53, Skp2, p27, Ki67, Bcl2 and p16-in correlation with histopathological changes. p16(INK4A) was not studied before in prophylactically removed ovaries. Methods. Ninety-four ovaries from 50 Ashkenazi Jewish BRCA carriers were compared with 42 ovaries removed for reasons unrelated to cancer and with 16 ovarian carcinomas. Results. Three (6%) patients from the high-risk group had an occult carcinoma. A significant association was found between BRCA-positive expression and the presence of atypical changes in the superficial ovarian epithelium (P = 0.014) as well as the presence of epithelial cortical clefts (P = 0.042). Expression of p53 in cortical inclusions was significantly higher in the BRCA-positive cases than in the benign control group (P = 0.03). The high-risk and the benign control group did not differ significantly by the expression of p16, BCL2, Ki67, p27 and SKP2 (P > 0.05). However, both groups significantly differed from the carcinoma group (P < 0.0001). A significant positive correlation was found between the expression of Ki67, and the grade of atypia in the high-risk group (R = 0.3, P = 0.01) and in the benign control group (R = 0.5, P = 0.02). Conclusions. BRCA mutation carriers had more atypical changes in the superficial epithelium (P = 0.014) and more epithelial cortical clefts (P = 0.042) compared to the benign control group. The histopathology changes were not supported by significantly altered expressions of the proteins used in our study. Additional molecular studies could contribute to the disclosure of precancerous ovarian lesions.