p53 nuclear protein overexpression in colorectal cancer: a dominant predictor of survival in patients with advanced hepatic metastases.

Abstract

PURPOSE To determine whether p53 protein expression is similar within primary colorectal cancer (CRC) and synchronous regional and distant metastases and to assess whether p53 nuclear protein expression could predict outcome in patients with synchronous unresectable liver metastases treated by hepatic artery infusional (HAI) chemotherapy. MATERIALS AND METHODS Paraffin sections from tumor and corresponding normal mucosa representative of 50 consecutive advanced CRC cases were examined for p53 nuclear protein expression by immunohistochemistry using the monoclonal antibody PAb 1801. Patterns of p53 nuclear expression were correlated with standard clinicopathologic variables and outcome, including response to HAI and survival. In a subset analysis, the pattern of nuclear p53 immunoreactivity was compared between primary CRC and lymph node and liver metastases. RESULTS Positive nuclear immunoreactivity for p53 protein was found in 72% of cases. The pattern of p53 protein expression in lymph node and liver metastases was identical to that of the primary tumor. The median survival time was 21.0 months in patients with p53-positive tumors and 53.2 months in patients with p53-negative tumors (Wilcoxon test P = .038). Two-year survival rates were 41.7% and 78.6%, respectively (P < .01). No significant difference was found in the response rates to HAI chemotherapy between the two groups. By multivariate analysis, p53 protein status was the single best predictor of survival, with a relative risk of 6.312. CONCLUSION Our results indicate that nuclear p53 protein status in primary CRC is similar to that in metastatic sites and may be the dominant predictor of survival in patients with advanced hepatic metastases.