P53 ACCUMULATION AND MUTATION ARE PROGNOSTIC INDICATORS OF POOR SURVIVAL IN HUMAN GASTIC CARCINOMA

The aim of our study was to examine the prognostic significance of p53 protein accumulation and gene mutation in a series of 116 gastric car cinomas from a low incidence population. Formalin-fixed, paraffin-embe dded tumour sections were used to investigate p53 protein accumulation by immunostaining with monoclonal antibody (MAb) DO-7 and p53 gene mu tation by single-strand conformation polymorphism analysis of exons 5- 8. Nuclear p53 accumulation was detected in 23% of tumours and mutatio n in 28%. Concordance between the 2 alterations was observed in 73% of cases. p53 protein accumulation was more frequent in tumours with lym ph node metastasis, while p53 mutations were more frequent in tumours from older patients. The histopathological parameters of depth of inva sion, grade and histological type showed no significant associations w ith either p53 alteration. In univariate analysis, both alterations we re associated with significantly shortened patient survival, The 5-yea r survival rate for patients with a p53 mutation was 9% compared to 42 % for those without a mutation. In multivariate analysis adjusted for the other histopathological parameters, p53 gene mutation but not immu nohistochemically-detected p53 protein accumulation was an independent prognostic indicator of poor survival in gastric carcinoma. (C) 1996 Wiley-Liss, Inc.