PROGNOSTIC VALUE OF TP53 AND K-RAS-2 MUTATIONAL ANALYSIS IN STAGE-IIICARCINOMA OF THE COLON

BACKGROUND: Genetic mutations involving oncogenes and tumor-suppressor genes occur in carcinogenesis, and may affect biologic behavior of ne oplasms. In this study, we analyzed the prognostic value of mutational analysis in colon carcinoma. PATIENTS AND METHODS: Archival pathology specimens from 70 consecutive patients, resected for stage III colon carcinoma, were analyzed for point mutations by amplification and dire ct sequencing of exons from the K-ras-2 and the TP53 genes (topographi c genotyping). Mutations were compared with adverse histopathologic fe atures (poor differentiation, vascular and lymphatic invasion, mucin p roduction) as prognostic markers. RESULTS: Five-year survival was 75% in patients with nonmutated lesions, significantly lower (21%) with TP 53 mutations (P = 0.01), and intermediate with K-ras-2 only (45%) or b oth K-ras-2 and TP53 mutations (36%), A TP53 mutation carried the high est relative risk of death (2.39; 95% confidence interval, 1.29 to 4.4 2; P = 0.006). There was an additive effect on the risk of death betwe en TP53 mutations and adverse histopathologic features. CONCLUSIONS: T he information derived from mutational analysis is creating new progno stic variables that may play a role in the choice of therapy for color ectal carcinoma.