Clinical Correlation of iNOS and p53 Expression in Colorectal Cancer

ABSTRACT

PURPOSE: Nitric oxide (NO) is synthesized from the amino acid L-arginine by nitric oxide synthase (NOS) which exists as three isoforms, the calcium-dependent endothelial NOS and neuronal NOS, and a calcium-independent inducible NOS. NO has been studied in a variety of human cancers and is implicated in both tumor promotion and inhibition. NO cause p53 mutation in human cells and mutations of p53 are the most common genetic abnormality yet found in human cancers. Aims of this study is to investigate the correlation of iNOS and p53 expression in colorectal cancer, and to evaluate its clinicopathological siginificance with the expression of these proteins. METHODS: 125 patients, who received curative resection of colorectal cancer from 1992 to 1996, were analyzed retrospectively. The monoclonal antibody to the iNOS (Transduction Laboratories.), the monoclonal antibody to the mutant p53 (Dako Co.) were used for the immunohistochemical analysis. Normal colorectal tissue were assayed in 45 cases. The relationship between mutant p53 and iNOS was investigated. RESULTS: When iNOS expression were detected in specimens, positive rate of mutant p53 were 72.4%. When mutant p53 expression were detected in specimens, positive rate of iNOS expression were 65.8%(P<0.05). Positive rate of iNOS, mutant p53 in tumor size were 51%, 56% below 4 cm and 60%, 63% in 4~8 cm and 47%, 67% above 8 cm. Positive rate of iNOS, mutant p53 in Dukes' stage were55%, 55% in stage B and 56%, 67% in stage C. Positive rate of iNOS, mutant p53 in histologic differentiation were 55%, 55% in well-differentiation and 61%, 66% in moderate differentiation and 35%, 48% in poor-differentiation. There was no difference in each Dukes stage between iNOS expression or p53 mutation and postop five year survival rate. Positive rate of iNOS, mutant p53 in normal tissue were 22%, 32%. CONCLUSION: The prevalence of iNOS expression and p53 mutation has been found in exceeding 50% of cases. There was a significant correlation between iNOS expression and p53 mutation in colorectal cancer. No correlation was found between iNOS expression or p53 mutation and clinicopathologic parameters.