ANALYSIS OF P53 GENE MUTATION BY POLYMERASE CHAIN REACTION-SINGLE STRAND CONFORMATION POLYMORPHISM PROVIDES INDEPENDENT PROGNOSTIC INFORMATION IN NODE-NEGATIVE BREAST-CANCER

Controversy continues regarding the prognostic utility of detection of p53 gene abnormalities in node-negative breast cancer. To resolve thi s, we used a rapid and nonisotopic PCR single strand conformation poly morphism method to screen for mutations in exons 4-8 of the p53 gene i n primary tumors from 422 node-negative breast cancer patients. The pr evalence of p53 mutation in the exons tested was 18%, p53 mutation was significantly associated with several markers of poor prognosis inclu ding larger tumor size, high tumor grade, low hormone receptor content , increased expression of MIB-1 (Ki-67), amplification of the HER-2/ne u oncogene, and accumulation of the p53 protein. After a median durati on follow-up period of 74 months, the parameters of tumor diameter gre ater than or equal to 20 mm, HER-2/neu oncogene amplification, and p53 mutation were found to be associated with a statistically significant shortened duration of disease-free and overall survival, but not the parameters of tumor grade, hormone receptor levels, or p53 expression, The poor prognosis associated with p53 mutation was observed primaril y in patients with a tumor diameter of greater than or equal to 20 mm, In multivariate analysis, p53 mutation was a risk factor for increase d risk of recurrence and death from breast cancer independent of tumor size, hormone receptor levels, HER-2/neu amplification, and MIB-1 exp ression. We conclude that a relatively simple and rapid single strand conformation polymorphism method of determining p53 mutation status in node-negative breast cancers can provide independent prognostic infor mation.