Tissue factor expression, angiogenesis, and thrombosis in pancreatic cancer
Tissue factor expression, angiogenesis, and thrombosis in pancreatic cancer
复制标题
DOI：
10.1158/1078-0432.ccr-06-2351
复制
发表时间：
2007-05-15
影响因子：
11.5
通讯作者：
Taubman, Mark B.
中科院分区：
文献类型：
--
作者：
Khorana, Alok A.;Ahrendt, Steven A.;Taubman, Mark B.
目的：止血激活在胰腺癌中很常见，可能与血管生成和静脉血栓栓塞有关。我们研究了组织因子（TF）在非侵袭性和侵袭性胰腺肿瘤中的表达，TF是凝血的主要起始物。我们相关TF表达与血管内皮生长因子（VEGF）的表达，微血管密度，静脉血栓栓塞切除pancreaticcancer.ExperimentalDesigns：从三个机构的回顾性系列患者的组织核心被用来建立组织微阵列。采用免疫组织化学方法对正常胰腺（n = 10）、导管内乳头状黏液性肿瘤（n = 70）、胰腺上皮内瘤变（n = 40）和切除或转移的胰腺腺癌（n = 130）中TF表达进行半定量分级。在大多数非侵袭性和侵袭性胰腺肿瘤中观察到TF表达，包括77%的胰腺上皮内瘤变，91%的导管内乳头状粘液性肿瘤和89%的胰腺癌，但在正常胰腺中没有。122例切除的胰腺癌中有66例（54%）发现TF高表达（定义为≥ 2级，中位数评分）。TF高表达的癌更可能同时表达VEGF（80%对TF低表达的27%，P < 0.0001），并且具有更高的中位MVD（每个组织核心8对TF低表达的5，P = 0.01）。TF高表达的胰腺癌患者的静脉血栓栓塞率为26.3%，而TF低表达的患者为4.5%（P = 0.04）。结论：TF表达发生在胰腺肿瘤转化的早期，与VEGF表达、微血管密度增加以及胰腺癌中可能的临床静脉血栓栓塞相关。前瞻性研究评估TF在胰腺癌预后中的作用是必要的。
Purpose: Hemostatic activation is common in pancreatic cancer and may be linked to angiogenesis and venous thromboembolism-We investigated expression of tissue factor (TF), the prime initiator of coagulation, in noninvasive and invasive pancreatic neoplasia. We correlated TF expression with vascular endothelial growth factor (VEGF) expression, microvessel density, and venous thromboembolism in resected pancreatic cancer.Experimental Design: Tissue cores from a tri-institutional retrospective series of patients were used to build tissue microarrays. TF expression was graded semiquantitatively using immunohistochemistry in normal pancreas (n = 10), intraductal papillary mucinous neoplasms (n = 70), pancreatic intraepithelial neoplasia (n = 40), and resected or metastatic pancreatic adenocarcinomas (n = 130).Results: TF expression was observed in a majority of noninvasive and invasive pancreatic neoplasia, including 77% of pancreatic intraepithelial neoplasias, 91% of intraductal papillary mucinous neoplasms, and 89% of pancreatic cancers, but not in normal pancreas. Sixty-six of 122 resected pancreatic cancers (54%) were found to have high TF expression (defined as grade >= 2, the median score). Carcinomas with high TF expression were more likely to also expressVEGF (80% versus 27% with low TF expression, P < 0.0001) and had a higher median MVD (8 versus 5 per tissue core with low TF expression, P = 0.01). Pancreatic cancer patients with high TF expression had a venous thromboembolism rate of 26.3% compared with 4.5% in patients with low TF expression (P = 0.04).Conclusions: TF expression occurs early in pancreatic neoplastic transformation and is associated with VEGF expression, increased microvessel density, and possibly clinical venous thromboembolism in pancreatic cancer. Prospective studies evaluating the role of TF in pancreatic cancer outcomes are warranted.