Prognostic significance of mutations in the p53 gene, particularly in the zinc-binding domains, in lymph node- and steroid receptor positive breast cancer patients

The aim of our study was to evaluate if p53 mutations, especially those in the L2/L3 domains of the p53 gene, add prognostic information for node-posi tive and steroid receptor positive breast cancer patients. Two hundred and five tumour samples from a randomised clinical trial of 596 lymph node- and steroid receptor positive breast cancer patients were included. All patien ts had been randomly allocated to receive 20 mg of adjuvant tamoxifen (TAM) daily for 2 years or TAM plus one cycle of low-dose, short-term chemothera py. For detection of p53 mutations we used in vitro amplification by polyme rase chain reaction and consecutively performed temperature gradient gel el ectrophoresis (PCR-TGGE) and direct sequencing. We found p53 mutations in 4 2/205 (20%) cases: 16/42 (38%) p53 mutations occurred within the L2/L3 doma ins of the p53 gene, and 26/42 (62%) outside the L2/L3 domains, p53 mutatio n served as a statistically significant parameter in predicting disease-fre e survival in univariate (P = 0.02) and multivariate (p = 0.009) analysis. For overall survival, no significant differences were observed. Patients wi th tumours that had p53 mutations within the L2/L3 domains of the gene show ed no significant difference to those with mutations outside the L2/L3 doma ins for disease-fi ee survival. For overall survival, mutations in the L2/L 3 domains showed a marginally significant difference (P = 0.05) in multivar iate analysis, but not in univariate analysis (P = 0.13). We conclude that mutation in the L2/L3 domains of the p53 gene is not an independent prognos tic indicator of disease outcome for patients suffering from breast cancer with lymph node metastases and positive steroid receptors, (C) 1999 Elsevie r Science Ltd. All rights reserved.