RELATIONSHIP AMONG P53, STAGE, AND PROGNOSIS OF LARGE-BOWEL CANCER

PURPOSE: We designed a study to determine whether increases in p53 pro tein in primary carcinomas of the colon or rectum correlate with overa ll survival. Mutations of the tumor suppressor gene p53 are detectable by immunocytochemical methods in colorectal cancers because of accumu lation of nuclear p53 protein. METHODS: IgG1 monoclonal antibody to hu man p53 protein (PAb 1801) was used to detect p53 in formalin-fixed, p araffin-embedded archival tumors resected from 84 patients with tumor limited to the bowel wall. A multivariate analysis was performed using five prognostic pathobiologic variables compared with the level of st aining of the p53 product. RESULTS: Nuclear p53 protein was observed i n 52 (62 percent) of 84 colorectal cancer patients with Stage T2 or T3 , N0, M0 disease. Patients with strong expression (3+ and 4+) of p53 a ppeared to die from their disease sooner than those with weak expressi on (1+ and 2+), although this was not statistically significant (P > 0 .59). Thirty-two patients did not express nuclear p53 by immunocytoche mical methods. When these patients were analyzed in combination with t he strong p53 expressors, the trend toward decreased survival increase d (P > 0.15). CONCLUSIONS: This data suggest that lack of p53 expressi on may also predict an adverse outcome in colorectal cancer. However, before the immunocytochemical method can be used clinically as a progn ostic indicator, the colorectal cancer patients with zero expression s hould be studied further to clarify the functional status of p53 in th eir tumors.