Alterations of the K-ras and p53 genes and microsatellite instability in sporadic colorectal carcinomas.

Background: The international guidelines for the evaluation of microsatellite instability (MSI) in colorectal cancer were defined in 1997 by the National Cancer Institute (NCI). Here, the relationship between MSI, cancer-associated genes and their clinicopathological variables were revaluated using these guidelines. Patients and Methods: Mutations of K-ras at exon 1 and p53 at exons 5, 6, 7 and 8 were analyzed in 43 cases of sporadic colorectal carcinoma. MSI was analyzed using the 5 markers recommended by the NCI reference panel, Results: The proportion of p53 mutations in the MSI-H cases (0 out of 5; 0%) was lower than that of non-MSI-H cases (23 out of 38; 60.5%) (p = 0.0117). The proportion of p53 mutations in microsatellite stable (MSS) cases (21 out of 34; 61.8%) was higher than that of non-MSS cases (2 out of 9; 22,2%) (p = 0.0366). The proportion of K-ras mutations in MSI-H tumors (1 out of 5; 20.0%) was less frequent than in non-MSI-H tumors (19 out of 38; 50.0%) (p = 0.2115). Conclusion: p53 mutations in MSI-H tumors were much less common than in non-MSI-H tumors. This result suggested that alterations of the p53 gene are not closely associated with carcinogenesis in MSI-H carcinomas.