OVEREXPRESSION OF P53 AND HER-2 NEU PROTEINS AS PROGNOSTIC MARKERS INEARLY-STAGE BREAST-CANCER/

Objective Overexpression of the p53 and HER-2/neu oncogenes are the tw o most common genetic abnormalities associated with breast cancer. Sho rter survival time has been reported in patients with tumors with p53 or HER-2/neu. This report analyzes a retrospective cohort of early sta ge breast cancers for both oncogenes and relates overexpression to cli nicopathologic parameters and survival. Methods Immunostaining for p53 and HER-2/neu was performed on 230 paraffin-embedded specimens of sta ge I and II breast cancers diagnosed and treated at Duke University Me dical Center between 1984 and 1987. Positive staining for both p53 and HER-2/neu in paraffin-embedded tissues indicates an underlying geneti c abnormality: point mutations in the p53 gene and amplification of th e HER-2/neu gene. Results In this cohort of patients, 24% were positiv e for p53 and 17% for HER-2/neu. Four per cent were positive for both oncogenes. Significant correlations were found between p53 immunostain ing and increasing tumor size, stage, and low estrogen and progesteron e receptor contents. Univariate analysis showed that p53 and HER-2/neu were indicators of overall and failure-free survival. An additive eff ect on survival was observed in patients with both oncogene abnormalit ies. Nodal status, HER-2/neu, and p53 all attained independent prognos tic value in a multivariate analysis. Conclusions The p53 and HER-2/ne u oncogenes have proven but limited prognostic value. An approach that combines several molecular genetic markers with established pathologi c criteria may help physicians to make more accurate predictions of pr ognosis in patients with early stage breast cancer.