Relationship among p53, stage, and prognosis of large bowel cancer.

PURPOSE

We designed a study to determine whether increases in p53 protein in primary carcinomas of the colon or rectum correlate with overall survival. Mutations of the tumor suppressor gene p53 are detectable by immunocytochemical methods in colorectal cancers because of accumulation of nuclear p53 protein.

METHODS

IgG1 monoclonal antibody to human p53 protein (PAb 1801) was used to detect p53 in formalin-fixed, paraffin-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 staining of the p53 product.

RESULTS

Nuclear p53 protein was observed in 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 appeared to die from their disease sooner than those with weak expression (1+ and 2+), although this was not statistically significant (P > 0.59). Thirty-two patients did not express nuclear p53 by immunocytochemical methods. When these patients were analyzed in combination with the strong p53 expressors, the trend toward decreased survival increased (P > 0.15).

CONCLUSIONS

This data suggest that lack of p53 expression may also predict an adverse outcome in colorectal cancer. However, before the immunocytochemical method can be used clinically as a prognostic indicator, the colorectal cancer patients with zero expression should be studied further to clarify the functional status of p53 in their tumors.