Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer

The aim of this study was to investigate the occurrence of (pre)neoplastic lesions in overtly normal Fallopian tubes from women predisposed to develop ing ovarian carcinoma. The presence of (pre)neoplastic lesions was scored i n histological specimens from 12 women with a genetically determined predis position for ovarian cancer, of whom seven tested positive for a germline B RCA1 mutation. A control group included 13 women. Immunohistochemistry was used to determine the expression of p21, p27, p53, cyclin A, cyclin DI, bcl -2, Ki67, HER-2/neu, and the oestrogen and progesterone receptors. Loss of heterozygosity (LOH) analysis on the BRCA1 locus was also assessed on dyspl astic tissue by PCR studies. Of the 12 women with a predisposition for ovar ian cancer, six showed dysplasia,: including one case of severe dysplasia. Five harboured hyperplastic lesions and in one woman no histological aberra tions were found in the Fallopian tube. No hyperplastic, dysplastic or neop lastic lesions were detected in the Fallopian tubes of control subjects. In the cases studied, morphologically normal tubal epithelium contained a hig her proportion of Ki67-expressing cells (p = 0.005) and lower fractions of cells expressing p2l (p < 0.0001) and p27 (p = 0.006) than in the control g roup. Even higher fractions of proliferating cells were found in dysplastic areas (p = 0.07) and accumulation of p53 was observed in the severely dysp lastic lesion. Expression patterns of other proteins studied, including the hormone receptors, were similar in cases and controls. One subject, a germ line BRCA1 mutation carrier, showed loss of the wild-type BRCAI allele in t he severely dysplastic lesion. In conclusion, the Fallopian tubes of women predisposed to developing ovarian cancer frequently harbour dysplastic chan ges, accompanied by changes in cell-cycle and apoptosis-related proteins, i ndicating an increased risk of developing tubal cancer. Copyright (C) 2001 John Wiley & Sons, Ltd.