TP53 and MYC gene alterations independently predict poor prognosis in breast cancer patients

✍ Scribed by Els M.J. J. Berns; Jan G. M. Klijn; Marcel Smid; Iris L. van Staveren; Maxime P. Look; Wim L. J. van Putten; John A. Foekens

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 792 KB
• Volume: 16
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/(sici)1098-2264(199607)16:3<170::aid-gcc3>3.0.co;2-w

✦ Synopsis

We intended to establish the frequency of exon-specific TP53 gene alterations and the relation t o patient and tumor characteristics and clinical outcome of patients with breast cancer. By using polymerase chain reaction-single-strand conformation polymorphism analysis (KR-SSCP) and sequencing techniques, TP53 gene alterations were found in 59 (32%) of the 187 samples studied. Most of the TP53 changes (37%) were observed in exon 7. In patients with known follow up (median, 107 months), there was no significant association of the frequency of TP53 mutation with menopausal or nodal status, tumor size, or progesterone receptor status. TP53 gene alterations were more frequently present in estrogen receptor (ER)-negative (ER-) tumors (P = 0.04) and in tumors with an amplified HERZ/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 with a TP53 gene mutation in exon 8 may be identified as having a particularly 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 TP53 gene alteration and MYC amplification independently predicted poor prognosis, with relative hazard rates for TP53 and MYC o f 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.