p53 and survival in early onset breast cancer: Analysis of gene mutations,loss of heterozygosity and protein accumulation

The p53 protein has proven to be central in tumorigenesis by its cell cycle regulatory properties and both gene mutations and protein accumulation hav e been associated with poor prognosis in breast cancer. The present study w as undertaken to investigate the prognostic significance of gene mutations, p53 protein accumulation and of loss of heterozygosity (LOH) at the TP53 l ocus in young (age < 37 years) breast cancer patients. In total, gene mutat ions were found in 21 of the 123 patients (17%), LOH in 20 of the 47 inform ative cases (43%) and protein accumulation in 47 of the 102 available cases (46%). Log rank analysis revealed no significant association between survi val and TP53 mutations tin general), p53 protein accumulation or LOH. Howev er, missense mutations localised to the zinc binding domain were significan tly (P= 0.0007) associated with poorer prognosis. As indicated in this as w ell as other studies, p53 protein accumulation is frequently found in young breast cancer patients, but this protein overexpression appears to be of m inor significance for survival. Nevertheless, the present report also sugge sts that specific mutations contribute substantially to tumour aggressivene ss. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.