Efficacy of hMLH1/hMSH2 Immunohistochemical Staining as Representative Index for Microsatellite Instability Status in Sporadic Colorectal Cancer

ABSTRACT

PURPOSE: Sporadic colorectal cancer with micosatellite instability (MSI) is supposed to have a distinct molecular profile, distinct clinocopathologic feature, and a distinct prognosis. However, the test for MSI is still expensive, and a big machine is needed for routine screening. This study was performed to examine the clinicopathologic of characteristics of MSI sporadic colorectal cancer and the efficacy of immunohistochemical staining for hMLH1 and hMSH2. METHODS: Five hundred sixty nine colorectal adenocarinomas resected from September 2003 to August 2004 at Asan Medical Center were prospectively collected. FAP (familial adenomatous polyposis), HNPCC (hereditary non-polyposis colo-rectal cancer), and incomplete tests of immunohistochemical staining or MSI were excluded. The MSI status was determined by using PCR (polymerase chain reaction). A first round of immunohistochemical staining for hMLH1/hMSH2 was performed, and a second round was performed for cases showing a disparity between the two exams. The clinicopathologic variables regarding the MSI status were analyzed, and the sensitivity and the specificity of immunohistochemical staining were evaluated. RESULTS: Sporadic colorectal cancers with MSI-H were 8.4% (n=48) and were associated with age (< or = 60 years), colorectal cancer familial history, synchronous colorectal cancer, right side tumor location, and poorly differentiated or mucinous cell type. However, age, synchronous colorectal cancer, and right side tumor location were associated an the multivariate analysis. In the first round of immunohistochemical staining, no expression of hMLH1 and/or hMSH2 was obserred in 71 cases (12.5%), and the sensitivity and the specificity were 50.0% and 91.9%, respectively. After repetitive immunohistochemical staining for the 71 cases showing disagreement with the to MSI status, the sensitivity and the specificity of the second round of immunohistochemical staining were 53.3% and 97.6%, respectively. CONCLUSIONS: Sporadic colorectal cancer with MSI appears to have distinct characteristics. However, immunohistochemical staining for hMLH1 and hMSH2 is not accurate enough to be used instead of MSI.