p53 and Ki-ras as prognostic factors for Dukes' stage B colorectal cancer

Mutations of the TP53 and Ki-ras genes have been reported to be of prognost ic importance in colorectal carcinomas. An increased intracellular concentr ation of the p53 protein, although not identical to, is sometimes seen in t umours with TP53 mutation and has been correlated with poor prognosis in so me tumour types. Previous colorectal cancer studies, addressing the prognos tic importance of Ki-ras mutation and TP53 aberrations, yielded contradicto ry results. The aim of this study was to determine in a clinically and ther apeutically homogeneous group of 122 sporadic Dukes' B colorectal carcinoma s with, a median follow-up of 67 months (3-144 months) whether or not p53 p rotein expression, TP53 mutation and K-ras mutation correlated with prognos is. p53 staining was performed by immunohistochemistry, using the monoclona l antibody DO7 on paraffin-embedded tissue. Mutations in exons 5-8 of the T P53 gene and in codons 12 and 13 of the K-ras gene were assayed in paraffin -embedded tissue by the single-strand conformation polymorphism (SSCP) assa y. Nuclear p53 staining was found in 57 (47%) tumours. Aberrant migration p atterns indicating mutation of the TP53 gene were found in 39 (32%) tumours . Forty-six carcinomas (38%) showed a mutation of the Ki-ras codons 12 or 1 3. In a univariate analysis, patients with wild-type TP53 status showed a t rend towards better survival, compared with those with mutated TP53 (log-ra nk test, P=0.051). Likewise, tumours immunohistochemically positive for p53 showed a worse prognosis than p53-negative tumours (P= 0.010f, The presenc e or absence of mutations in Ki-,as did not correlate with prognosis (P=0.7 03). In multivariate analysis, only p53 immunoreactivity emerged as an inde pendent marker for prognosis hazard ratio (HR)=2.16, 95% confidence interva l (CI) 1.12-4.11, P=0.02). Assessment of p53 protein expression is more dis criminative than TP53 mutation to predict the outcome of Dukes' stage B tum ours and could be a useful tool to identify patients who might benefit from adjuvant therapy. (C) 2000 Published by Elsevier Science Ltd. All rights r eserved.