Expression of heat shock proteins (HSP27, HSP60, HSP70, HSP90, GRP78, GRP94) in hepatitis B virus-related hepatocellular carcinomas and dysplastic nodules

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, glucoseregulated 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 HBVrelated hepatocarcinogenesis. GRP78, GRP94, and HSP90 may be important prognostic markers of HBV-related HCC, strongly suggesting vascular invasion and intrahepatic metastasis.

Diagnosis of gastric epithelial neoplasia:Dilemma for Korean pathologists

The histopathological diagnosis of gastric mucosal biopsy and endoscopic mucosal resection/endoscopic submucosal dissection specimens is important,but the diagnostic criteria,terminology,and grading system are not the same in the East and West.A structurally invasive focus is necessary to diagnose carcinoma for most Western pathologists,but Japanese pathologists make a diagnosis of cancer based on severe dysplastic cytologic atypia irrespective of the presence of invasion.Although the Vienna classification was introduced to reduce diagnostic discrepancies,it has been difficult to adopt due to different concepts for gastric epithelial neoplastic lesions.Korean pathologists experience much difficulty making a diagnosis because we are influenced by Japanese pathologists as well as Western medicine.Japan is geographically close to Korea,and academic exchanges are active.Additionally,Korean doctors are familiar with Western style medical terminology.As a result,the terminology,definitions,and diagnostic criteria for gastric intraepithelial neoplasia are very heterogeneous in Korea.To solve this problem,the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists has made an effort and has suggested guidelines for differential diagnosis:(1) a diagnosis of carcinoma is based on invasion;(2) the most important characteristic of low grade dysplasia is the architectural pattern such as regular distribution of crypts without severe branching,budding,or marked glandular crowding;(3) if nuclear pseudostratification occupies more than the basal half of the cryptal cells in three or more adjacent crypts,the lesion is considered high grade dysplasia;(4) if severe cytologic atypia is present,careful inspection for invasive foci is necessary,because the risk for invasion is very high;and(5) other structural or nuclear atypia should be evaluated to make a final decision such as cribriform pattern,papillae,ridges,vesicular nuclei,high nuclear/cytoplasmic ratio,loss of nuclear polarity,thick and irregular nuclear membrane,and nucleoli.