Possible correlation between iron deposition and enhanced proliferating activity in hepatitis C virus-positive hepatocellular carcinoma in Myanmar (Burma).
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.
Soe
Kyaw
K
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.
Hishikawa
Yoshitaka
Y
Fukuzawa
Yoshitaka
Y
Win
Ne
N
Yin
Khine San
KS
Win
Khin Maung
KM
Myint
Aye Aye
AA
Koji
Takehiko
T
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
D053222:Fas Ligand Protein; D007501:Iron