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Deficient expression ofO 6-Methylguanine-DNA methyltransferase combined with mismatch-repair proteins hMLH1 and hMSH2 is related to poor prognosis in human biliary tract carcinoma

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Abstract

Background

O 6-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that transfers methyl groups fromO 6-methylguanine to itself. Alkylation of DNA at theO 6 position of guanine is an important step in the induction of mutations in the organism by alkylating agents. TheO 6-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.

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Authors and Affiliations

  1. Department of Surgery, Saga Medical School, Nabeshima 5-1-1, 849-850, Saga, Japan

    Naohiko Kohya MD, Kohji Miyazaki MD, PhD, Shiroh Matsukura MD, Hiroyuki Yakushiji MD, PhD, Yoshihiko Kitajima MD, PhD & Kenji Kitahara MD, PhD

  2. Department of Biochemistry Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

    Masao Fukuhara MD, PhD & Yusaku Nakabeppu PhD

  3. Department of Biology, Fukuoka Dental College, Fukuoka, Japan

    Mutsuo Sekiguchi MD, PhD

Authors
  1. Naohiko Kohya MD
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  2. Kohji Miyazaki MD, PhD
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  3. Shiroh Matsukura MD
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  4. Hiroyuki Yakushiji MD, PhD
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  7. Masao Fukuhara MD, PhD
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  9. Mutsuo Sekiguchi MD, PhD
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Correspondence to Kohji Miyazaki MD, PhD.

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Kohya, N., Miyazaki, K., Matsukura, S. et al. Deficient expression ofO 6-Methylguanine-DNA methyltransferase combined with mismatch-repair proteins hMLH1 and hMSH2 is related to poor prognosis in human biliary tract carcinoma. Annals of Surgical Oncology 9, 371–379 (2002). https://doi.org/10.1007/BF02573872

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