Abnormal expression of HSP gp96 associated with HBV replication in human hepatocellular carcinoma.
BACKGROUND
Heat shock protein (HSP) gp96 is a member of the HSP90 family and presumably overexpresses as a result of stimulation by mutated or abnormal proteins. Its abnormal expression correlates with carcinogenesis, progression and prognosis of hepatocellular carcinoma (HCC). In this study, we investigated the pathological characteristics of liver gp96 expression and its relationship with hepatitis B virus (HBV) replication in HCC patients.


METHODS
Tumor specimens were prospectively collected from 30 HCC patients undergoing liver resection. Total RNAs were extracted from HCC or their non-cancerous tissues. The distribution of gp96 expression in hepatocytes was investigated by streptavidin peroxidase (S-P) immunohistochemistry and tissue HBV-DNA was detected by the in situ molecular hybridization technique. The association of gp96 expression with HBV replication, and the histopathological characteristics of HCC were analyzed.


RESULTS
The gp96 was strongly expressed in HCC (73.3%, 22 of 30) and weakly (46.7%, 14 of 30) in non-cancerous tissues. The gp96 expression in HCC tissues was correlated with degree of tumor differentiation and tumor size, but not with tumor number (P>0.05). Immunohistochemical analysis showed that 17 of 19 HCC patients with HBV-DNA-positive were strongly expressed for gp96, whereas only 5 of 11 patients with HBV-DNA-negative were positive for gp96. A significant difference was found between the two groups (89.5% vs. 45.5%, P<0.05).


CONCLUSIONS
The abnormal expressions of HSP gp96 in HCC tissues are associated with HBV replication. This finding indicates that HBV infection plays an important role in the development of HCC.
Yao
Deng-Fu
DF
The Institute of Clinical Medicine, Nantong University, Nantong 226001, China. yaodf@ahnmc.com
Wu
Xin-Hua
XH
Su
Xiao-Qin
XQ
Yao
Min
M
Wu
Wei
W
Qiu
Li-Wei
LW
Zou
Li
L
Meng
Xian-Yong
XY
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000821:virology*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008113:Liver Neoplasms / Q000378:metabolism* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D014779:Virus Replication
D004279:DNA, Viral; D006360:Heat-Shock Proteins