Deficient expression of O6-methylguanine-DNA methyltransferase combined with mismatch-repair proteins hMLH1 and hMSH2 is related to poor prognosis in human biliary tract carcinoma

Naohiko Kohya, Kohji Miyazaki, Shiroh Matsukura, Hiroyuki Yakushiji, Yoshihiko Kitajima, Kenji Kitahara, Masao Fukuhara, Yusaku Nakabeppu, Mutsuo Sekiguchi

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53 Citations (Scopus)

Abstract

Background: O6-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that transfers methyl groups from O6-methylguanine to itself. Alkylation of DNA at the O6 position of guanine is an important step in the induction of mutations in the organism by alkylating agents. The O6-methyl G:T mismatch is recognized by the mismatch-repair (MMR) pathway. The biliary duct is highly exposed to alkylating agents because of its anatomical location. Methods: We examined 39 surgically resected gallbladder carcinomas and 35 extrahepatic bile duct carcinomas and evaluated the expression of MGMT and MMR protein (hMLH1 and hMSH2) by immunohistochemical staining. Results: MGMT-negative staining was detected in 59.0% of gallbladder carcinoma specimens and 60.0% of extrahepatic bile duct carcinoma specimens. In gallbladder carcinoma, hMLH1 and hMSH2-negative staining was observed in 51.3% and 59.0%, respectively, whereas in extrahepatic bile duct carcinoma, the respective values were 57.1% and 65.7%. MGMT-negative staining correlated with hepatic invasion in gallbladder carcinoma and with poor prognosis in both types of tumor. Furthermore, a combined MGMT and MMR status was shown to be a more significant prognostic biomarker in both tumor types. Conclusions: Combined MGMT and MMR is a possible prognostic marker that probably reflects an accumulation of genetic mutations.

Original languageEnglish
Pages (from-to)371-379
Number of pages9
JournalAnnals of Surgical Oncology
Volume9
Issue number4
DOIs
Publication statusPublished - May 21 2002

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

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