Expression and prognostic roles of beta-catenin in hepatocellular carcinoma: correlation with tumor progression and postoperative survival.

肝细胞癌 免疫组织化学 细胞周期蛋白D1 病理 肿瘤进展 连环素 六氯环己烷 连环蛋白 医学 BETA(编程语言) 癌症研究 生物 癌症 内科学 细胞周期 Wnt信号通路 信号转导 程序设计语言 生物化学 计算机科学
作者
Satoshi Inagawa,Michio Itabashi,Shinya Adachi,Toru Kawamoto,Masao Hori,Jun Shimazaki,Fuyo Yoshimi,Katashi Fukao
出处
期刊:PubMed 卷期号:8 (2): 450-6 被引量:74
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Although hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the human liver, the molecular changes and mechanisms that regulate its development and progression remain unclear. In the present study, we investigated the correlation between beta-catenin expression and clinical outcome in 51 patients with relatively small (maximal diameter < 30 mm), solitary HCCs.The tumors were classified according to histological tumor differentiation (grade I, 11 tumors; grade II, 28 tumors; grade III, 12 tumors). Using immunohistochemical methods to detect nuclear accumulation of beta-catenin, we investigated the correlation between beta-catenin expression and clinical outcome and compared the correlation with cyclin D1, Ki-67, and E-cadherin.Focal or generalized nuclear beta-catenin expression was observed in 36.4% (4 of 11) of the grade I tumors, 39.3% (11 of 28) of the grade II tumors, and 25% (3 of 12) of the grade III tumors. Nuclear beta-catenin-positive grade III tumors were associated with significantly poorer survival (P = 0.004), whereas none of the patients with nuclear beta-catenin-negative grade I tumors died. With regard to proliferative activity, positive nuclear beta-catenin staining correlated significantly with an increased Ki-67 labeling index in grade I (P < 0.0001) and grade III (P = 0.0045) tumors and with reduced epithelial cadherin expression in the cell membrane (P < 0.001). In contrast, no association with the expression of cyclin D1, one of the target factors of beta-catenin, was detected.Our present data suggest that beta-catenin plays important roles in promoting tumor progression by stimulating tumor cell proliferation and reducing the activity of cell adhesion systems and is associated with a poor prognosis, especially in patients with poorly differentiated HCCs.

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