title: Prognostic significance of tissue factor in pancreatic ductal adenocarcinoma.
abstract: 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.
authors.affiliation: Pathology, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nitori
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ino
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: Tesshi
authors.initials: T
authors.lastname: Yamada
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Honda
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Tomoo
authors.initials: T
authors.lastname: Kosuge
authors.forename: Yae
authors.initials: Y
authors.lastname: Kanai
authors.forename: Masaki
authors.initials: M
authors.lastname: Kitajima
authors.forename: Setsuo
authors.initials: S
authors.lastname: Hirohashi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D013925:Thromboplastin / Q000032:analysis* / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D034741:RNA, Small Interfering; D013925:Thromboplastin