Usefulness of immunohistochemical staining for p53 in the prognosis of breast carcinomas: correlations with established prognosis parameters and with the proliferation marker, MIB-1

Abstract

Mutations of the p53 gene often result in the overexpression of p53 protein. Previous studies have suggested that the function of p53 and its mutant protein forms may be linked with the disease course of patients with a breast carcinoma. In the present study, we tested 462 primary breast carcinomas for the presence of p53 antigen using immunohistochemical methods employing antibodies against the clone, DO-1. These tumors were also immunohistochemically stained using the monoclonal antibody, MIB-1, in order to demonstrate the presence of Ki67. Comparison of the presence of p53 with other prognostic parameters revealed highly significant negative correlations with estrogen- and progesterone-receptor status (P < 0.001 and P = 0.001, respectively) as well as positive correlations with both the presence of MIB-1 (P < 0.001) and the histological grading (P = 0.008). The presence of p53 was not correlated with tumor stage and node status. Evaluation of the findings for all 462 tumors as well as for node-positive and -negative subgroups revealed less favorable findings for overall survival and the disease-free period for both p53-positive tumors (for total group, overall survival, P = 0.0002, disease-free period, P = 0.02; for node-positive group, overall survival, P = 0.0004, disease-free period, P = 0.1045) and breast carcinomas with higher proportions of cell nuclei positive for MIB-1 (total, overall survival, P = 0.0026, disease-free period, P = 0.0022; node-positive, overall survival, P = 0.021, disease-free period, P = 0.0882). We were able to demonstrate that p53 expression in breast carcinomas means a significantly worse prognosis for grade II tumors (overall survival, P = 0.0002; disease-free period, P = 0.0116), for overall survival in the case of estrogen-receptor-positive tumors (P = 0.014), and for tumors showing increased proliferation activity (overall survival, P = 0.0477).