COX-2 and iNOS Expression and Microvessel Density by Microsatellite Instability in Colorectal Cancer

ABSTRACT

PURPOSE: We tried to identify the overall incidence of microsatellite instability (MSI) and the utility of mismatch repair (MMR) protein expression in sporadic colorectal cancers in Korean. We also investigate the role of angiogenesis in colorectal cancers by MSI status. METHODS: A total 85 resected colorectal cancers were submitted for MSI study using PCR methods with 5 markers and immunohistochemistry (IHS) for hMLH1 and hMSH2. Expression of COX-2 and iNOS and microvessel density by IHS were correlated with various clinicopathologic prognostic factors. RESULTS: Among 85 cases of sporadic colorectal cancers, MSI was observed in 11 cases (12.9%) including 10 MSI-H and 1 MSI-L cases. Patients with MSI (+) showed female prevalence (1.75 : 1), low Dukes stage, mucinous histologic type, and Crohn-like lymphoid reaction than those with MSS. Overall sensitivity of hMLH1 and/or hMSH2 expression was 98.6% and specificity was 72.7%. iNOS expression was significantly correlated with COX-2 expression in tumor cells (P=0.006), however, they were not correlated with MSI status. High microvessel density was correlated with hMLH1 expression (P=0.025), COX-2 expression (P= 0.05), and Crohn-like lymphoid reaction (P=0.041). CONCLUSIONS: IHS for MMR proteins is a valuable substitute of MSI status and COX-2 related neoangiogenesis is thought to be related to inhibition of microsatellite unstable colorectal cancer progression via decreased microvessel density.