Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Clin Cancer Res. 2009 Nov 15;15(22):6830-40. doi: 10.1158/1078-0432.CCR-09-0371. Epub 2009 Oct 27.
Despite the strong association between malignant disease and thromboembolic disorders, the molecular and cellular basis of this relationship remains uncertain. We evaluated the hypothesis that tumor-derived tissue factor-bearing microparticles in plasma contribute to cancer-associated thrombosis.
We developed impedance-based flow cytometry to detect, quantitate, and size microparticles in platelet-poor plasma. We evaluated the number of tissue factor-bearing microparticles in a cohort of cancer patients of different histologies (N = 96) and conducted a case-control study of 30 cancer patients diagnosed with an acute venous thromboembolic event (VTE) compared with 60 cancer patients of similar age, stage, sex, and diagnosis without known VTE, as well as 22 patients with an idiopathic VTE.
Tissue factor-bearing microparticles were detected in patients with advanced malignancy, including two thirds of patients with pancreatic carcinoma. Elevated levels of tissue factor-bearing microparticles were associated VTE in cancer patients (adjusted odds ratio, 3.72; 95% confidence interval, 1.18-11.76; P = 0.01). In cancer patients without VTE, a retrospective analysis revealed a 1-year cumulative incidence of VTE of 34.8% in patients with tissue factor-bearing microparticles versus 0% in those without detectable tissue factor-bearing microparticles (Gray test P = 0.002).The median number of tissue factor-bearing microparticles in the cancer VTE cohort (7.1 x 10(4) microparticles/microL) was significantly greater than both the idiopathic VTE and cancer-no VTE groups (P = 0.002 and P = 0.03, respectively). Pancreatectomy in three patients eliminated or nearly eliminated these microparticles which coexpressed the epithelial tumor antigen, MUC-1.
We conclude that tumor-derived tissue factor-bearing microparticles are associated with VTE in cancer patients and may be central to the pathogenesis of cancer-associated thrombosis.
尽管恶性肿瘤与血栓栓塞性疾病之间存在很强的关联性，但这种关联的分子和细胞基础仍不确定。我们评估了一个假说，即血浆中来源于肿瘤的组织因子携带微粒在癌症相关血栓形成中起作用。
我们开发了基于阻抗的流式细胞术来检测、定量和测量血小板贫血浆中的微粒。我们评估了不同组织学类型癌症患者队列中的组织因子携带微粒数量（N=96），并对 30 例确诊为急性静脉血栓栓塞事件（VTE）的癌症患者进行了病例对照研究，将其与 60 例年龄、分期、性别和诊断相似但无已知 VTE 的癌症患者以及 22 例特发性 VTE 患者进行了比较。
在晚期恶性肿瘤患者中检测到组织因子携带微粒，包括三分之二的胰腺癌患者。组织因子携带微粒水平升高与癌症患者的 VTE 相关（校正比值比，3.72；95%置信区间，1.18-11.76；P=0.01）。在无 VTE 的癌症患者中，回顾性分析显示，组织因子携带微粒的患者 1 年内 VTE 的累积发生率为 34.8%，而无检测到组织因子携带微粒的患者为 0%（Gray 检验 P=0.002）。癌症 VTE 组的组织因子携带微粒中位数（7.1x10(4)个微粒/微升）明显高于特发性 VTE 组和癌症无 VTE 组（P=0.002 和 P=0.03）。在 3 例患者中，胰腺切除术消除或几乎消除了这些同时表达上皮肿瘤抗原 MUC-1 的微粒。
我们得出结论，肿瘤来源的组织因子携带微粒与癌症患者的 VTE 相关，可能是癌症相关血栓形成发病机制的核心。
