OBJECTIVE: To evaluate the impact of p53 gene mutations on long-term survival in patients with intermediate stage carcinoma of the colon. DESIGN: 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. Archival pathology specimens were analyzed for point mutations of exons from the p53 gene by means of amplification and direct sequencing by polymerase chain reaction. MAIN OUTCOME MEASURES: The impact of p53 mutations and of adverse histopathologic features (i.e., poor differentiation, lymphovascular invasion, or mucin production) on patient survival. RESULTS: Median overall survival was 64 months (95 months for patients with stage II and 34 months for patients with stage III colon carcinoma; P = .001). Presence of a p53 mutation was the single most important risk factor associated with poorer survival in both patients with stage II (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 in 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 of death between p53 mutations and adverse histopathologic variables. CONCLUSIONS: The presence of p53 mutations carries an independent adverse prognostic value in colon cancer. These findings imply that the applicability of mutational analysis in clinical practice is likely to affect therapeutic choices in the future.
OBJECTIVE: To evaluate the impact of p53 gene mutations on long-term survival in patients with intermediate stage carcinoma of the colon. DESIGN: 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. Archival pathology specimens were analyzed for point mutations of exons from the p53 gene by means of amplification and direct sequencing by polymerase chain reaction. MAIN OUTCOME MEASURES: The impact of p53 mutations and of adverse histopathologic features (i.e., poor differentiation, lymphovascular invasion, or mucin production) on patient survival. RESULTS: Median overall survival was 64 months (95 months for patients with stage II and 34 months for patients with stage III colon carcinoma; P = .001). Presence of a p53 mutation was the single most important risk factor associated with poorer survival in both patients with stage II (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 in 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 of death between p53 mutations and adverse histopathologic variables. CONCLUSIONS: The presence of p53 mutations carries an independent adverse prognostic value in colon cancer. These findings imply that the applicability of mutational analysis in clinical practice is likely to affect therapeutic choices in the future.
Authors: K R Aupperle; D L Boyle; M Hendrix; E A Seftor; N J Zvaifler; M Barbosa; G S Firestein Journal: Am J Pathol Date: 1998-04 Impact factor: 4.307