Microsatellite Instability and Mismatch Repair Protein (hMLH1, hMSH2) Expression in Intrahepatic Cholangiocarcinoma

ABSTRACT

BACKGROUND: To clarify the role of the mismatch repair (MMR) system in the carcinogenesis of intrahepatic cholangiocarcinoma (ICC), we investigated the microsatellite instability (MSI) status and MMR protein expression in ICC. METHODS: Thirty-six cases of ICCs were examined by microsatellite analysis for 55 markers that encompassed all of the chromosomal arms and BAT26. An immunohistochemical study for hMLH1 and hMSH2 was also performed. RESULTS: Widespread MSI (MSI-H) accompanied with a loss of hMLH1 expression was found in one case (2.8%). This MSI-H case was an adenosquamous carcinoma showing intraductal tubulopapillary adenocarcinoma and invasive adenosquamous carcinoma component. Loss of hMLH1 was noted in both components while the frequency and shifted band patterns of MSI were not identical between the components. Another 10 ICCs (27.8%) revealed low level MSI with preserved MMR gene expression. CONCLUSIONS: Our data suggested that a genetic defect in the MMR system and MSI is not a major pathway in the carcinogenesis of ICC.