Hui A M, Cui X, Makuuchi M, Li X, Shi Y Z, Takayama T
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Hepatology. 1999 Nov;30(5):1167-73. doi: 10.1002/hep.510300506.
This study was undertaken to identify potential abnormalities of p27(Kip1) and cyclin D1 expression in extrahepatic bile duct carcinomas and to assess the prognostic significance of p27(Kip1) and cyclin D1 levels for patients with this disease. Decreased p27(Kip1) expression (<50% nuclei staining) and cyclin D1 overexpression (>5% nuclei staining) was observed immunohistochemically in 19 (56%) and 23 (68%) of the 34 tumors examined, respectively. Both decreased p27(Kip1) and cyclin D1 overexpression were associated with relapse (P =.0005 for p27(Kip1) and P =.0004 for cyclin D1). Kaplan-Meier curves showed that both decreased p27(Kip1) and cyclin D1 overexpression correlate significantly with shortened survival rates (for p27(Kip1), P =.0419 and P =.002 for overall and disease-free survival; for cyclin D1, P =.0392 and P =.0021 for overall and disease-free survival). Cox regression model analyses identified decreased p27(Kip1) and cyclin D1 overexpression as independent markers predicting death from relapse (P =.0371, risk ratio: 3.891 for p27(Kip1); P =.0429, risk ratio: 8.31 for cyclin D1). Decreased p27(Kip1) was associated with cyclin D1 overexpression (P =.0202), and coincident abnormalities of the 2 proteins occurred in 16 of the 34 (47%) tumors, indicating that extrahepatic bile duct carcinoma progression may require synchronous dysfunction of p27(Kip1) and cyclin D1 in about half of patients. Patients with tumors showing coincident abnormalities of p27(Kip1) and cyclin D1 showed even more frequent recurrence than patients with an alteration in only 1 of the 2 proteins. In conclusion, decreased p27(Kip1) expression and cyclin D1 overexpression, alone and in combination, predict poor prognosis in patients with resectable extrahepatic bile duct carcinoma.
本研究旨在确定肝外胆管癌中p27（Kip1）和细胞周期蛋白D1表达的潜在异常，并评估p27（Kip1）和细胞周期蛋白D1水平对该疾病患者的预后意义。在34例接受检查的肿瘤中，分别有19例（56%）和23例（68%）通过免疫组织化学观察到p27（Kip1）表达降低（<50%细胞核染色）和细胞周期蛋白D1过表达（>5%细胞核染色）。p27（Kip1）降低和细胞周期蛋白D1过表达均与复发相关（p27（Kip1）的P = 0.0005，细胞周期蛋白D1的P = 0.0004）。Kaplan-Meier曲线显示，p27（Kip1）降低和细胞周期蛋白D1过表达均与缩短的生存率显著相关（对于p27（Kip1），总生存和无病生存的P分别为0.0419和0.002；对于细胞周期蛋白D1，总生存和无病生存的P分别为0.0392和0.0021）。Cox回归模型分析确定p27（Kip1）降低和细胞周期蛋白D1过表达是预测复发死亡的独立标志物（p27（Kip1）的P = 0.0371，风险比：3.891；细胞周期蛋白D1的P = 0.0429，风险比：8.31）。p27（Kip1）降低与细胞周期蛋白D1过表达相关（P = 0.0202），34例肿瘤中有16例（47%）出现这两种蛋白的同时异常，表明在大约一半的患者中，肝外胆管癌进展可能需要p27（Kip1）和细胞周期蛋白D1的同步功能障碍。p27（Kip1）和细胞周期蛋白D1同时异常的肿瘤患者比仅一种蛋白发生改变的患者复发更频繁。总之，p27（Kip1）表达降低和细胞周期蛋白D1过表达单独或联合出现，均预示可切除肝外胆管癌患者预后不良。
