MUTATED P53 GENE IS AN INDEPENDENT ADVERSE PREDICTOR OF SURVIVAL IN COLON-CARCINOMA

Objective: evaluate the impact of p53 gene mutations on long-term surv ival in patients with intermediate stage carcinoma of the colon. Desig n: Retrospective cohort study; median follow-up of 87 months. Setting: Tertiary care academic medical center. Patients: Mutational analysis was conducted in a single institution in 141 consecutive patients with resected stage II (n=71) and stage III (n=70) colon carcinoma. Archiv al pathology specimens were analyzed for point mutations of exons from the p53 gene by means of amplification and direct sequencing by polym erase chain reaction. Main Outcome Measures: The impact of p53 mutatio ns and of adverse histopathologic features (ie, poor differentiation, lymphovascular invasion, or mucin production) on patient survival. Res ults: Median overall survival was 64 months (95 months for patients wi th stage II and 34 months for patients with stage III colon carcinoma; P=.001). Presence of a p53 mutation was the single most important ris k factor associated with poorer survival in both patients with stage I I (P=.02) and stage III colon carcinoma (P=.006) throughout the follow -up period. A p53 mutation increased the risk of death by 2.82 times i n patients with stage II and by 2.39 times in patients with stage III colon carcinoma. There was an additive effect on the cumulative risk o f death between p53 mutations and adverse histopathologic variables. C onclusions: The presence of p53 mutations carries an independent adver se prognostic value in colon cancer. These findings imply that the app licability of mutational analysis in clinical practice is likely to af fect therapeutic choices in the future.