Detection of hepatitis C virus RNA in hepatocellular carcinoma by in situ hybridization.
BACKGROUND
Hepatocellular carcinoma frequently is associated with chronic hepatitis C virus (HCV) infection. The presence of HCV in hepatocellular carcinoma has been detected by reverse-transcription polymerase chain reaction of antigenomic HCV RNA, a tissue-specific replicative form of the virus. Now, however, this method of detecting the presence of HCV has been invalidated by reports of antigenomic RNA in the blood or in peripheral blood mononuclear cells.


METHODS
In situ hybridization of HCV RNA was conducted with digoxigenin-labeled cDNA from the core region on surgical specimens of noncancerous and cancerous areas from 12 patients with chronic hepatitis C with or without cirrhosis associated with hepatocellular carcinoma. Several control experiments were also performed, including RNase digestion before hybridization, hybridization with the use of a negative control, and immunohistochemical staining of HCV-core protein.


RESULTS
The in situ hybridization showed positive signals both in noncancerous and cancerous areas of the liver tissue in eight cases. Positive signals were confined to neoplastic cells and nonneoplastic hepatocytes. There were fewer HCV-positive cells in the cancerous area than in the surrounding noncancerous area.


CONCLUSIONS
In situ detection of HCV presents direct evidence of HCV infection in the neoplastic cells of hepatocellular carcinoma and suggests that neoplastic cells may lose their affinity for HCV in the course of malignant transformation.
Tang
L
L
Second Department of Internal Medicine, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
Tanaka
Y
Y
Enomoto
N
N
Marumo
F
F
Sato
C
C
D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000473:pathology / Q000821:virology*; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D018076:DNA, Complementary / Q000235:genetics; D004076:Digoxigenin; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D006526:Hepatitis C / Q000150:complications / Q000473:pathology; D006521:Hepatitis, Chronic / Q000150:complications / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008099:Liver / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000150:complications / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000150:complications / Q000473:pathology / Q000821:virology*; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis*; D012260:Ribonucleases; D014158:Transcription, Genetic; D014758:Viral Core Proteins / Q000032:analysis
D018076:DNA, Complementary; D012367:RNA, Viral; D014758:Viral Core Proteins; D012260:Ribonucleases; D004076:Digoxigenin