title: Loss of p16(INK4) protein, alone and together with loss of retinoblastoma protein, correlate with hepatocellular carcinoma progression.
abstract: To investigate the role of p16(INK4) protein absence in hepatocellular carcinoma progression, we examined p16(INK4) expression immunohistochemically in 81 primary and 23 metastatic lesions of hepatocellular carcinoma, in which retinoblastoma protein status had been determined. p16(INK4) protein was absent from 44% of the total of 104 tumors. The rate of p16(INK4) absence was twice as high in metastatic lesions (74%) compared with primary lesions (36%) (P=0.001). Loss of p16(INK4) and/or retinoblastoma protein was significantly associated with decreased tumor differentiation, vascular invasion and metastasis. In conclusion, p16(INK4) protein absence, alone and together with loss of retinoblastoma protein, contributes to hepatocellular carcinoma progression.
authors.affiliation: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan. amhui-tky@umin.ac.jp
authors.forename: A M
authors.initials: AM
authors.lastname: Hui
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Shi
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: T
authors.initials: T
authors.lastname: Takayama
authors.forename: M
authors.initials: M
authors.lastname: Makuuchi
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002453:Cell Cycle; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D016160:Retinoblastoma Protein / Q000378:metabolism*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein