Jpn. J. Infect. Dis., 56, 12-18, 2003

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Original Article

Geographic Characterization of Hepatitis Virus Infections, Genotyping of Hepatitis B Virus, and p53 Mutation in Hepatocellular Carcinoma Analyzed by In Situ Detection of Viral Genomes from Carcinoma Tissues: Comparison among Six Different Countries

Xin Ding¹, Young Nyun Park², Teresa Casanovas Taltavull³, Swan N. Thung⁴, Xiaoming Jin⁵, Yi Jin⁶, Nguyen Sao Trung⁷, Yoshihiro Edamoto^1,8, Tetsutaro Sata¹ and Kenji Abe¹*

¹Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, ⁶Department of Pathology, Nagoya University Graduate School of Medicine, Aichi 466-8550, ⁸Division of Surgery, International Medical Center of Japan, Tokyo 162-8655, Japan, ²Department of Pathology, Yonsei University College of Medicine, Seoul, Korea, ³Liver and Kidney Transplant Unit, Hospital of Bellvitge, Barcelona, Spain, ⁴Department of Pathology, The Mount Sinai Medical Center of the City University of New York, New York, USA, ⁵Department of Pathology, Harbin Medical University, Harbin, China and ⁷Department of Pathology, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam

(Received January 15, 2003. Accepted February 7, 2003)

SUMMARY: We investigated the relationship of infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) to p53 mutation in hepatocellular carcinomas (HCC) from six countries, including Japan, China, Korea, Vietnam, Spain, and the Unites States. For this purpose, we used formalin-fixed, paraffin-embedded liver tissues obtained from 449 patients with HCC to detect the viral and p53 genes by polymerase chain reaction (PCR). HBV was the most prevalent in Korea (69.1%), China (66.1%), Vietnam (60.5%), and Spain (38.6%). In contrast, HCV was the most prevalent in Japan (59.8%) and in the United States (41.5%). Type C of HBV was the most common genotype (78.6%) encountered in HCC in these countries. Importantly, among 125 intrahepatic HBV DNA-positive patients, 44 (35.2%) were serologically negative for HBsAg (occult hepatitis B). Based on PCR, immunohistochemical, serological, and clinical findings, 4.8% of HCC patients were diagnosed with non-B, non-C. A point mutation at exon 7 of p53 was detected in 20 of the 239 HCC samples examined, including those from 9 Chinese, 5 American, 2 Japanese, 2 Korean, and 2 Spanish patients, respectively. Interestingly, a point mutation with an amino acid substitution at codon 251 (Ile→Asn) was detected frequently in 11 of 20 (55%) cases. A specific mutation induced by Aflatoxin B1 at codon 249 was seen in two patients, both Chinese. Our results suggest that genotype C of HBV may play an important role in hepatocarcinogenesis in different geographic regions, and that in situ detection of HBV genomes could be important for clarifying the agent(s) of unknown etiology related to HCC.

*Corresponding author: Mailing address: Department of Pathology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan. Tel: +81-3-5285-1111 ext. 2624, Fax: +81-3-5285-1189, E-mail: kenjiabe@nih.go.jp

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