P53 PROTEIN EXPRESSION IN BREAST-CANCER AS RELATED TO HISTOPATHOLOGICAL CHARACTERISTICS AND PROGNOSIS

Formalin-fixed, paraffin-embedded biopsies of 193 women with primary breast cancer followed-up for over 10 years were analysed immunohistochemically for the expression of p53 protein. Altogether, 58% (113/193) of the tumors were positive for p53 protein. Over-expression of p53 was associated with the ductal type, high-grade tumors, dense stromal inflammatory cell infiltrate, high S-phase fraction, high mitotic frequency and high values of the nuclear factors. In univariate analysis, intense p53 over-expression predicted a poor outcome, whereas a short recurrence.-free survival (RFS) was related to p53 negativity. In axillary lymph-node-negative (ANN) tumors, p53 negativity was related to short RFS, and in axillary lymph-node-positive (ANP) tumors this inverse relationship was statistically significant. In Cox's analysis, p53 protein over-expression had no independent prognostic value comparable with the well-established prognostic factors. However, p53 protein accumulation was an independent indicator of long RFS in the entire cohort, in ANP tumors and in rapidly proliferating tumors. The results indicate a dual role for p53 protein over-expression in breast cancer prognosis. The low survival probability associated with intensively p53-positive tumors is probably related to rapid cancer-cell proliferation, whereas the long RFS of p53-positive tumors might be explained by the development of circulating antibodies to p53 protein. The role of p53 protein in breast cancer is incompletely understood, and the p53 gene should be subjected to detailed analysis of specific mutations. (C) 1993 Wiley-Liss, Inc.