title: Possible correlation between iron deposition and enhanced proliferating activity in hepatitis C virus-positive hepatocellular carcinoma in Myanmar (Burma).
abstract: BACKGROUND
  The aim of this study was to survey the effect of deposited iron on the cell kinetics of hepatitis C virus (HCV)-positive hepatocellular carcinoma (HCC) in Myanmar (Burmese) patients.
  
  
  METHODS
  Formalin-fixed and paraffin-embedded liver tissues from 34 Myanmar patients with HCC were used. To detect iron deposition, Prussian blue staining was performed. Cell proliferation and apoptosis were assessed by Ki-67 staining and by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) assay, respectively. HCV RNA was detected by in situ hybridization, and HCV protein, Fas and Fas ligand (FasL) were localized by immunohistochemistry. To identify the subtype of lymphocytes, CD8 was used as a surface marker.
  
  
  RESULTS
  Iron deposition was found in 43% of the HCC cases, and was heavier in moderately differentiated HCC than in well-differentiated HCC. The Ki-67 labeling index (LI) in cancer cells was higher in Prussian blue-positive-HCC than in -negative HCC (3.8 +/- 2.2 vs 1.5 +/- 1.7, mean +/- SD; P=0.0067), whereas there was no significant difference between these groups in TUNEL LI. HCV protein was localized in cancer cells, and was found in 89% of the patients. In addition, Fas was expressed in HCC cells, and FasL was localized in HCC cells as well as in infiltrating CD8+ T lymphocytes. The frequency of apoptosis of HCC cells was correlated significantly with the population density of infiltrating CD8+ T lymphocytes.
  
  
  CONCLUSIONS
  Our results indicated that, in Myanmar patients with HCC, iron deposition might accelerate hepatocarcinogenesis, by promoting cancer cell proliferation, without affecting the Fas/FasL apoptotic system.
authors: Department of Histology and Cell Biology, Unit of Basic Medical Science, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
authors: Kyaw
authors: K
authors: Soe
authors: Yoshitaka
authors: Y
authors: Hishikawa
authors: Yoshitaka
authors: Y
authors: Fukuzawa
authors: Ne
authors: N
authors: Win
authors: Khine San
authors: KS
authors: Yin
authors: Khin Maung
authors: KM
authors: Win
authors: Aye Aye
authors: AA
authors: Myint
authors: Takehiko
authors: T
authors: Koji
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000821:virology; D049109:Cell Proliferation; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007501:Iron / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000821:virology; D008297:Male; D008875:Middle Aged; D002052:Myanmar
chemical_list: D053222:Fas Ligand Protein; D007501:Iron