Liver Cancer
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2005; 11(14): 2072-2079
Published online Apr 14, 2005. doi: 10.3748/wjg.v11.i14.2072
Expression of heat shock proteins (HSP27, HSP60, HSP70, HSP90, GRP78, GRP94) in hepatitis B virus-related hepatocellular carcinomas and dysplastic nodules
Seung Oe Lim, Sung Gyoo Park, Jun-Hi Yoo, Young Min Park, Hie-Joon Kim, Kee-Taek Jang, Jae Won Cho, Byung Chul Yoo, Gu-Hung Jung, Cheol Keun Park
Seung Oe Lim, Sung Gyoo Park, Jun-Hi Yoo, Guhung Jung, School of Biological Sciences, Seoul National University, Seoul, Korea
Young Min Park, Hepatology Center and Laboratory of Hepatocarcinogenesis, Bundang Jesaeng General Hospital, Kyungkido, Korea
Hie-Joon Kim, School of Chemistry, Seoul National University, Seoul, Korea
Kee-Taek Jang, Cheol Keun Park, Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Jae Won Cho, General Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Byung Chul Yoo, Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Author contributions: All authors contributed equally to the work.
Supported by the fund from the Korea Science and Engineering Foundation (Grant No. R01-2001-00098). Seung Oe Lim was supported by BK21 Research Fellowship from the Ministry of Education and Human Resources Development
Correspondence to: Cheol Keun Park, MD, PhD, Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea. ckpark@smc.samsung.co.kr
Telephone: +82-2-3410-2766 Fax: +82-2-3410-0025
Received: October 5, 2004
Revised: October 6, 2004
Accepted: December 8, 2004
Published online: April 14, 2005
Abstract

AIM: Expression of heat shock proteins (HSPs) is frequently up-regulated in hepatocellular carcinoma (HCC), which evolves from dysplastic nodule (DN) and early HCC to advanced HCC. However, little is known about the differential expression of HSPs in multistep hepatocarcinogenesis. It was the purpose of this study to monitor the expression of HSPs in multistep hepatocarcinogenesis and to evaluate their prognostic significance in hepatitis B virus (HBV)-related HCC.

METHODS: Thirty-eight HCC and 19 DN samples were obtained from 52 hepatitis B surface antigen-positive Korean patients. Immunohistochemical and dot immunoblot analyses of HSP27, HSP60, HSP70, HSP90, glucose regulated protein (GRP)78, and GRP94 were performed and their expression at different stages of HCC development was statistically analyzed.

RESULTS: Expression of HSP27, HSP70, HSP90, GRP78, and GRP94 increased along with the stepwise progression of hepatocarcinogenesis. Strong correlation was found only in GRP78 (Spearman’s r = 0.802). There was a positive correlation between the expressions of GRP78, GRP94, HSP90, or HSP70 and prognostic factors of HCC. Specifically, the expression of GRP78, GRP94, or HSP90 was associated significantly with vascular invasion and intrahepatic metastasis.

CONCLUSION: The expressions of HSPs are commonly up-regulated in HBV-related HCCs and GRP78 might play an important role in the stepwise progression of HBV-related hepatocarcinogenesis. GRP78, GRP94, and HSP90 may be important prognostic markers of HBV-related HCC, strongly suggesting vascular invasion and intrahepatic metastasis.

Keywords: Heat shock protein; Hepatocellular carcinoma; Dysplastic nodule; Hepatocarcinogenesis; Immunohisto-chemistry; Dot immunoblot analysis