Proliferative activity and p53 over-expression of ovarian epithelial tumors.

Proliferative activity (PA) and p53 over-expression were assessed in 68 cases of primary ovarian epithelial tumors of variable grades of malignancy by immunohistochemical methods using antibodies to PCNA (proliferative cell nuclear antigen) and p53 molecule. First, we compared the values in benign tumors, tumors of borderline malignancy and malignant tumors. Malignant tumors possessed higher PA value (26.8 +/- 14.7%) than benign tumors (1.6 +/- 1.4%), and tumors of borderline malignancy exhibited an intermediate value (11.4 +/- 5.1%). Intranuclear accumulations of p53 product were more frequently observed in malignant tumors (16/32, 50%) than in tumors of borderline malignancy (3/9, 33%). None of the benign tumors exhibited p53 over-expression. In malignant tumors, PA correlated well with the histologic grade of tumors, although the histologic type and stage of the diseases did not correlate significantly with PA. Then, we focussed on the cases of malignant ovarian cancer composed of heterogeneous lesions showing a different grade of malignancy; invasive lesion (IL), non-invasive lesion (NIL), and benign appearing lesion (BAL). PA of NIL was almost identical with that of IL (19.6 +/- 13.5% vs. 23.3 +/- 12.6%), while BAL showed significantly lower PA (2.1 +/- 3.0%, p < 0.001) than the above two lesions and was similar to that of benign tumors. Furthermore, p53 over-expression was never observed in BAL, even in cases in which IL and/or NIL showed p53 over-expression. Thus, the results indicated that histologically benign-appearing lesions of malignant ovarian epithelial tumors possessed a biologic character similar to benign tumors. Collectively, all these findings would support the concept that a part of malignant ovarian epithelial tumors would be derived from benign tumors through progressive transformation.