Prognostic significance of tissue factor in pancreatic ductal adenocarcinoma

被引:146
作者
Nitori, N
Ino, Y
Nakanishi, Y
Yamada, T
Honda, K
Yanagihara, K
Kosuge, T
Kanai, Y
Kitajima, M
Hirohashi, S
机构
[1] Natl Canc Ctr, Res Inst, Div Pathol, Chuo Ku, Tokyo 1040045, Japan
[2] Natl Canc Ctr, Res Inst, Chemotherapy Div, Tokyo 1040045, Japan
[3] Natl Canc Ctr, Res Inst, Cent Anim Lab, Tokyo 1040045, Japan
[4] Natl Canc Ctr, Dept Surg, Tokyo, Japan
[5] Keio Univ, Sch Med, Dept Surg, Tokyo 160, Japan
关键词
D O I
10.1158/1078-0432.CCR-04-0866
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Tissue factor (TF) is a transmembrane glycoprotein that plays roles in the blood coagulation and intracellular signaling pathways, and has also been suggested to modulate the biological behavior of cancer cells. In order to examine the clinicopathologic significance of TF expression in pancreatic ductal adenocarcinoma, TF expression was determined by immunohistochemistry using a newly raised anti-TF monoclonal antibody in 113 patients who had undergone surgical resection of pancreatic ductal adenocarcinoma. According to the incidence of tumor cell immunopositivity, patients were divided into "negative TF (0%), "weak TF (<25%), or "high TF (25% or more) groups, which accounted for 11.6% (n = 13), 44.2% (n = 50), and 44.2% (n = 50) of the total, respectively. Increased TF expression was correlated with the extent of the primary tumor (P = 0.0043), lymph node metastasis (P = 0,0043), lymphatic distant metastasis (P 0.0039), advanced tumor-node-metastasis stage (P = 0.0002),and high tumor grade (P 0,0164). Multivariate analysis using the Cox proportional hazards model showed that high TF expression was an independent negative predictor for survival (hazard ratio, 2.014; P = 0.0076). Moreover, patients with TF-negative tumors had a significantly better prognosis even if lymph node metastasis was present (P < 0.0001). We also showed that TF knockdown by RNA interference suppressed the invasiveness of a pancreatic adenocarcinoma cell line in vitro. These results indicate that TF expression may contribute to the aggressiveness of pancreatic ductal adenocarcinoma by stimulating tumor invasiveness, and that evaluation of the primary tumor for TF expression may identify patients with a poor prognosis.
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收藏
页码:2531 / 2539
页数:9
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