title: Overexpression of clusterin in human hepatocellular carcinoma.
abstract: Clusterin has been reported to play a significant role in tumorigenesis, and its overexpression occurs in various human malignancies. We examine the clusterin overexpression in human hepatocellular carcinoma (HCC) and verify its clinical usefulness as a candidate biomarker by clinicopathologic and survival analysis. We examined clusterin overexpression immunohistochemically in 100 surgically resected HCCs using the tissue microarray method. A total of 89 HCCs exhibited clusterin overexpression, in 2 distinct staining patterns, cytoplasmic (n=35) and canalicular (n=54). Clusterin positivity demonstrated an inverse correlation with tumor cell apoptosis evaluated by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay (P=0.024). Within the clusterin-positive group, cytoplasmic overexpression had a positive correlation with tumor cell proliferative activity measured by the Ki-67 labeling index (P=0.003). HCCs demonstrating cytoplasmic clusterin overexpression were associated with poor Edmondson's histological grade and high TNM stage (P <0.05). In the survival analysis, the cytoplasmic-positive group demonstrated an overall poorer prognosis than the canalicular-positive group, according to univariate and multivariate analysis (P <0.05). In HCC, clusterin may play an important role in tumorigenesis and progression, corresponding to its subcellular localization. Cytoplasmic clusterin overexpression could be a potential new prognostic marker for the aggressiveness of HCC.
authors.affiliation: Department of Pathology, Inje University, Seoul Paik Hospital, Korea.
authors.forename: Yun Kyung
authors.initials: YK
authors.lastname: Kang
authors.forename: Seong Woo
authors.initials: SW
authors.lastname: Hong
authors.forename: Hyucksang
authors.initials: H
authors.lastname: Lee
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D051152:Clusterin; D018450:Disease Progression; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006498:Hepatectomy; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000378:metabolism*; D009367:Neoplasm Staging; D040081:Protein Array Analysis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones