title: DNA damage sensor γ -H2AX is increased in preneoplastic lesions of hepatocellular carcinoma.
abstract: BACKGROUND
  Phosphorylated histone H2AX ( γ -H2AX) is a potential regulator of DNA repair and is a useful tool for detecting DNA damage. To evaluate the clinical usefulness of γ -H2AX in hepatocellular carcinoma (HCC), we measured the level of γ -H2AX in HCC, dysplastic nodule, and nontumorous liver diseases.
  
  
  METHODS
  The level of γ -H2AX was measured by immunohistochemistry in fifty-eight HCC, 18 chronic hepatitis, 22 liver cirrhosis, and 19 dysplastic nodules. Appropriate cases were also examined by fluorescence analysis and western blotting. results: All cases with chronic liver disease showed increased levels of γ -H2AX expression. In 40 (69.9%) of 58 cases with HCC, the labeling index (LI) of γ -H2AX was above 50% and was inversely correlated with the histological grade. Mean γ -H2AX LI was the highest in dysplastic nodule (74.1 ± 22.1%), which was significantly higher than HCC (P < 0.005). Moreover, γ -H2AX was significantly increased in nontumorous tissues of HCC as compared with liver cirrhosis without HCC (62.5 ± 24.7%, from 5.1 to 96.0%, P < 0.005).
  
  
  CONCLUSIONS
  γ -H2AX was increased in the preneoplastic lesions of HCC and might be a useful biomarker for predicting the risk of HCC.
authors.affiliation: Department of Medical Technology, Niigata University Graduate School of Health Sciences, 2-746 Asahimachi-dori, Niigata 951-8518, Japan. yasunobu@med.niigata-u.ac.jp
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Wakai
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kubota
authors.forename: Mami
authors.initials: M
authors.lastname: Osawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Takamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamagiwa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Aoyagi
authors.forename: Ayumi
authors.initials: A
authors.lastname: Sanpei
authors.forename: Shun
authors.initials: S
authors.lastname: Fujimaki
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000378:metabolism; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D004249:DNA Damage; D005260:Female; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000378:metabolism; D008113:Liver Neoplasms / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; C468783:H2AX protein, human; D006657:Histones