Loss of heterozygosity at the RB-1 locus and pRB immunostaining in epithelial ovarian tumors: A molecular, immunohistochemical, and clinicopathologicstudy

Alterations in the retinoblastoma gene (RB-1) are common in human neoplasia . The frequency of loss of heterozygosity (LOH) at the RB-1 locus on chromo some 13q14 was studied in a series of 51 epithelial ovarian tumors (10 beni gn, 7 borderline, and 34 malignant). LOH was scored by the absence or reduc tion of the signal to < 50% of one of the alleles in tumor DNA compared wit h normal DNA. LOH results were correlated with retinoblastoma protein (pRB) immunostaining. LOH at the RB-1 locus was observed in 9 tumors (17.6%), sp ecifically in 1 of 7 borderline tumors and 8 of 34 ovarian carcinomas (23.5 %). Among the malignant tumors, LOH occurred more frequently in carcinomas with serous differentiation (7/23; 30%). A heterogeneous (10% to 70% cells) or diffuse (> 70% cells) pRB immunostaining was less frequent in benign (1 /10; 10%) and borderline (2/7; 28%) tumors than in ovarian carcinomas (15/3 4; 44%), an observation that correlated with the higher proliferative index in carcinomas than in benign and borderline tumors. However, lack or only focal (< 10% cells) pRB immunostaining occurred in the vast majority of tum ors with LOH at the RB-1 locus (7/9; 77%), a finding that may suggest a tum or suppressor role for RB-1 in these tumors. The results suggest that RB-I may play a role in a subset of ovarian carcinomas, particularly those exhib iting serous differentiation.