title: Expression of transforming growth factor-beta1 and transforming growth factor-beta receptors in hepatocellular carcinoma and dysplastic nodules.
abstract: In this study we analyzed by immunohistochemistry the expression of TGF-beta1 protein and TGF-beta receptors I and II in 4 low-grade dysplastic nodules, 2 high-grade dysplastic nodules, 6 early, 22 small, and 62 advanced hepatocellular carcinomas. The expression of TGF-beta1 protein by hepatocytes was decreased in advanced hepatocellular carcinoma compared with small or early hepatocellular carcinoma(P < .05). Frequent and intense staining of TGF-beta1 protein was noted in the sinusoidal endothelium of advanced hepatocellular carcinomas despite of its decreased staining in hepatocellular carcinoma cells. Reduced expression of TGF-beta receptors I and II compared with surrounding nontumorous tissue were noted from the early hepatocellular carcinoma stage suggesting that down-regulation of TGF-beta receptors is correlated with progression from premalignant to malignant phenotype. Reduced expression of both TGF-beta1 and TGF-beta receptor II in neoplastic hepatocytes were also significantly correlated with increased tumor size and increased proliferative activity(P < .05). These findings suggest that during hepatocarcinogenesis, the inhibitory effects of TGF-beta1 protein on hepatocellular carcinoma cells is outweighed by its effects on stromal elements, which, overall, contributes indirectly to a tumor growth stimulatory environment. Also, the growth-inhibitory effects of TGF-beta1 may have been further negated by reduced TGF-beta receptors on hepatocellular carcinoma cells.
authors.affiliation: Department of Pathology and Brian Korea 21 Project for Medical Science, Yonsei University, College of Medicine, Seoul, South Korea.
authors.forename: So Ya
authors.initials: SY
authors.lastname: Paik
authors.forename: Young Nyun
authors.initials: YN
authors.lastname: Park
authors.forename: Hoguen
authors.initials: H
authors.lastname: Kim
authors.forename: Chanil
authors.initials: C
authors.lastname: Park
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D020518:Focal Nodular Hyperplasia / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
chemical_list: D019394:Ki-67 Antigen; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1