Objective: The genetic changes in hereditary ovarian cancer syndromes suggest that the phenotype of ovarian surface epithelium in women with familial ovarian cancer might be altered. To test this hypothesis, we compared two tumor markers, CA 125 and 2G3, in cultures of overtly normal epithelium from patients with and without familial ovarian cancer.
Study design: Surface epithelia from 18 patients with no family history of ovarian cancer, five with family histories that were insufficient to be classified as familial, and seven with strong family histories were examined by immunofluorescence, immunocytochemistry, and radioimmunoassay. The influence of cell density, morphologic features, propagation in culture, and immortalization with SV40 on the expression of the markers was investigated.
Results: CA 125 occurred in cells with epithelial rather than atypical morphologic features. In cultures with no family history and minor family history, CA 125 was present in up to 45% cells in passage 1 but in only < 5% cells in 14 of 16 cultures by passages 3 to 4. In contrast, nine of 10 cultures with family history retained > 5% CA 125-positive cells in passages 3 to 4. This prolonged presence of CA 125 correlated with a persisting epithelial phenotype, whereas most cells with no family history and minor family history became atypical by passage 3. Immortalization eliminated CA 125 in all three types of cells. 2G3 bound to few cells in low passage, independent of family history and morphologic features. The proportion of 2G3-expressing cells increased significantly with immortalization in all cultures, independent of family history. Ovarian carcinoma lines expressed both markers.
Conclusion: In cultures of ovarian surface epithelium 2G3 expression increases with immortalization, whereas CA 125 is lost with immortalization but correlates with epithelial cell morphologic features and with family history. The results suggest that there may be phenotypic changes in overtly normal ovarian surface epithelium of women with family histories of ovarian cancer.