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World J Gastroenterol. Jan 7, 2008; 14(1): 70-75
Published online Jan 7, 2008. doi: 10.3748/wjg.14.70
Genetic changes of p53, K-ras, and microsatellite instability in gallbladder carcinoma in high-incidence areas of Japan and Hungary
Masayuki Nagahashi, Yoichi Ajioka, Istvan Lang, Zoltan Szentirmay, Miklos Kasler, Hiroto Nakadaira, Naoyuki Yokoyama, Gen Watanabe, Ken Nishikura, Toshifumi Wakai, Yoshio Shirai, Katsuyoshi Hatakeyama, Masaharu Yamamoto
Masayuki Nagahashi, Yoichi Ajioka, Gen Watanabe, Ken Nishikura, Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
Istvan Lang, Department of Medical Oncology “B”, National Institute of Oncology, Budapest H-1122, Hungary
Zoltan Szentirmay, Department of Molecular Pathology, National Institute of Oncology, Budapest H-1122, Hungary
Miklos Kasler, Department of Head and Neck Surgery, National Institute of Oncology, Budapest H-1122, Hungary
Hiroto Nakadaira, Department of Nursing, Faculty of Nursing, Social Welfare, and Psychology, Niigata Seiryo University, Niigata 951-8510, Japan
Naoyuki Yokoyama, Toshifumi Wakai, Yoshio Shirai, Katsuyoshi Hatakeyama, Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
Masaharu Yamamoto, Department of Community Preventive Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
Correspondence to: Yoichi Ajioka, MD, PhD, Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan. ajioka@med.niigata-u.ac.jp
Telephone: +81-25-2272098
Fax: +81-25-2270760
Received: August 15, 2007
Revised: September 22, 2007
Published online: January 7, 2008
Abstract

AIM: To disclose geographic differences in genetic changes involved in gallbladder carcinogenesis between two distinct high-incidence areas of Japan and Hungary.

METHODS: We examined 42 cases of gallbladder carcinoma: 22 Japanese and 20 Hungarian cases. p53 mutations at exons 5 to 8 and K-ras mutations at codon 12 were tested by direct sequencing. Microsatellite instability was determined from fluorescent dye-labeled PCR amplifications of five-microsatellite markers (BAT-25, BAT-26, D2S123, D5S346, and D17S250).

RESULTS: Mutations of p53 were detected in 11 of 22 Japanese cases and 6 of 18 Hungarian cases (11/22 vs 6/18, P = 0.348). Transition at CpG sites was found in none of 11 Japanese cases and 2 of 6 Hungarian cases; the difference was marginally significant (0/11 vs 2/6, P = 0.110). K-ras mutations were detected in only one of the Hungarian cases. Eight of 19 (42.1%) Japanese cases were MSI-high (presence of novel peaks in more than one of the five loci analyzed), whereas only 1 of 15 (6.7%) Hungarian cases was MSI-high (P = 0.047).

CONCLUSION: It appears that the p53 mutations and MSI differ in patients with gallbladder carcinoma between two distinct high-incidence areas. Geographic variation might exist in the process of gallbladder carcinogenesis.

Keywords: Gallbladder, Gallbladder Neoplasms, K-ras, Microsatellite instability, p53