Yao Jorge L, Ryan Charlotte K, Francis Charles W, Kohli Manish, Taubman Mark B, Khorana Alok A
Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA. jorge
Cancer Invest. 2009 May;27(4):430-4. doi: 10.1080/07357900802527247.
Tissue factor (TF) is the principal physiologic initiator of coagulation. It also plays an important role in tumor growth and metastasis possibly by contributing to angiogenesis. We evaluated the expression of TF in benign and malignant prostate tissue and correlated it with the expression of the pro-angiogenic protein, vascular endothelial growth factor (VEGF). We used a tissue microarray (TMA) constructed from 80 archival prostatectomy specimens. Core samples were collected from benign prostate tissue (BP) (n= 77), high-grade prostatic intraepithelial neoplasia (PIN) (n= 26), and carcinoma (PCa) (n= 93). TMA sections were stained with an immunopurified polyclonal TF antibody and a rabbit polyclonal VEGF. Two pathologists manually scored staining in epithelial cells using the German Immunoreactive Score. Positive staining for TF was seen predominantly in PCa with rare positive glands in BP and PIN. TF expression was significantly lower in BP versus PCa specimens (p< .001) and in PIN versus PCa specimens (p< .001). Positive staining for VEGF was seen in PCa, BP, and PIN. Rates of VEGF expression were also significantly lower in BP versus PCa specimens (p= .003) but not in PCa versus PIN (p= .430). The majority of PCa samples positive for TF were also positive for VEGF (p< .001). Our findings reinforce the link between angiogenesis and TF expression in PCa. We suggest further exploration of TF-mediated pathways leading to increased tumor aggressiveness in PCa, and the possible use of anti-TF agents in PCa.
组织因子(TF)是凝血的主要生理启动因子。它可能通过促进血管生成在肿瘤生长和转移中也发挥重要作用。我们评估了TF在良性和恶性前列腺组织中的表达,并将其与促血管生成蛋白血管内皮生长因子(VEGF)的表达相关联。我们使用了由80份存档前列腺切除标本构建的组织微阵列(TMA)。从良性前列腺组织(BP)(n = 77)、高级别前列腺上皮内瘤变(PIN)(n = 26)和癌(PCa)(n = 93)中采集核心样本。TMA切片用免疫纯化的多克隆TF抗体和兔多克隆VEGF染色。两名病理学家使用德国免疫反应评分系统对上皮细胞中的染色进行手动评分。TF的阳性染色主要见于PCa,BP和PIN中仅有罕见的阳性腺体。与PCa标本相比,BP中TF表达显著降低(p <.001),与PCa标本相比,PIN中TF表达也显著降低(p <.001)。PCa、BP和PIN中均可见VEGF的阳性染色。与PCa标本相比,BP中VEGF表达率也显著降低(p =.003),但PCa与PIN相比则无显著差异(p =.430)。大多数TF阳性的PCa样本VEGF也呈阳性(p <.001)。我们的研究结果强化了PCa中血管生成与TF表达之间的联系。我们建议进一步探索导致PCa肿瘤侵袭性增加的TF介导途径,以及抗TF药物在PCa中的可能应用。