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

Formalin-fixed, paraffin-embedded biopsies of 193 women with primary b reast cancer followed-up for over 10 years were analysed immunohistoch emically for the expression of p53 protein. Altogether, 58% (113/193) of the tumors were positive for p53 protein. Over-expression of p53 wa s associated with the ductal type, high-grade tumors, dense stromal in flammatory cell infiltrate, high S-phase fraction, high mitotic freque ncy and high values of the nuclear factors. In univariate analysis, in tense p53 over-expression predicted a poor outcome, whereas a short re currence.-free survival (RFS) was related to p53 negativity. In axilla ry lymph-node-negative (ANN) tumors, p53 negativity was related to sho rt RFS, and in axillary lymph-node-positive (ANP) tumors this inverse relationship was statistically significant. In Cox's analysis, p53 pro tein over-expression had no independent prognostic value comparable wi th the well-established prognostic factors. However, p53 protein accum ulation was an independent indicator of long RFS in the entire cohort, in ANP tumors and in rapidly proliferating tumors. The results indica te a dual role for p53 protein over-expression in breast cancer progno sis. The low survival probability associated with intensively p53-posi tive tumors is probably related to rapid cancer-cell proliferation, wh ereas the long RFS of p53-positive tumors might be explained by the de velopment of circulating antibodies to p53 protein. The role of p53 pr otein in breast cancer is incompletely understood, and the p53 gene sh ould be subjected to detailed analysis of specific mutations. (C) 1993 Wiley-Liss, Inc.