TP53 AND MYC GENE ALTERATIONS INDEPENDENTLY PREDICT POOR-PROGNOSIS INBREAST-CANCER PATIENTS

We intended to establish the frequency of exon-specific TP53 gene alte rations and the relation to patient and tumor characteristics and clin ical outcome of patients with breast cancer. By using polymerase chain reaction-single-strand conformation polymorphism analysis (PCR-SSCP) and sequencing techniques, TP53 gene alterations were found in 59 (32% ) of the 187 samples studied. Most of the TP53 changes (37%) were obse rved in exon 7. In patients with known follow up (median, 107 months), there was no significant association of the frequency of TP53 mutatio n with menopausal or nodal status, tumor size, or progesterone recepto r status. TP53 gene alterations were more frequently present in estrog en receptor (ER)-negative (ER(-)) tumors (P = 0.04) and in tumors with an amplified HER2/NEU oncogene (P = 0.03). Univariate analysis showed that patients with a mutated TP53 in their primary tumors had shorter relapse-free (P = 0.01) and overall (P = 0.03) survival. Patients wit h a TP53 gene mutation in exon 8 may be identified as having a particu larly rapid rate of relapse. In Cox multivariate regression analysis, which included age, menopausal status, lymph node status, tumor size, steroid-hormone-receptor status, and oncogene amplifications, both TP5 3 gene alteration and MYC amplification independently predicted poor p rognosis, with relative hazard rates for TP53 and MYC of 1.8 and 1.6, respectively in analysis for relapse-free survival and of 1.7 and 1.6, respectively in analysis for overall survival. (C) 1996 Wiley-Liss, I nc.