Seto S, Onodera H, Kaido T, Yoshikawa A, Ishigami S, Arii S, Imamura M
Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Cancer. 2000 Jan 15;88(2):295-301. doi: 10.1002/(sici)1097-0142(20000115)88:2<295::aid-cncr8>3.0.co;2-u.
It has been suggested that tissue factor (TF) plays an important role in tumor metastasis. Its expression in sarcoma cells was reported to up-regulate the vascular endothelial growth factor (VEGF) gene and thereby enhance tumor angiogenesis, which is essential to tumor metastasis. Although many malignant tumors have been reported to express this protein constitutively, recent clinical studies have focused mainly on the correlations among TF expression, tumor progression, and histologic grade. Therefore, to address the role of TF and the underlying mechanism of hematogenous metastasis of colorectal carcinoma, the authors analyzed the correlations among TF expression, hepatic metastasis, and VEGF gene expression in surgical specimens. Furthermore, they analyzed the prognostic significance of TF expression with respect to overall patient survival.
Expression of TF and VEGF genes in 67 advanced colorectal carcinoma specimens was studied by immunohistochemistry and Northern blot analysis, respectively. The correlations among TF expression, hepatic metastasis, and other factors were analyzed with univariate and multivariate statistics. Survival rates were calculated using the Kaplan-Meier method.
Univariate and multivariate analyses showed TF expression to be a significant (P = 0.0001) and independent risk factor for hepatic metastasis, whereas a weak but insignificant correlation was observed between TF and VEGF gene expression. The outcomes in the TF positive group were significantly worse in all cases (P = 0.0001) and in the cases without synchronous hepatic metastasis (P = 0.0156).
Although the precise mechanisms are unknown, TF expression is a suitable indicator of both hepatic metastasis and prognosis for colorectal carcinoma patients.
有研究表明组织因子（TF）在肿瘤转移中起重要作用。据报道，其在肉瘤细胞中的表达上调血管内皮生长因子（VEGF）基因，从而增强肿瘤血管生成，而这对肿瘤转移至关重要。尽管已有报道称许多恶性肿瘤可组成性表达该蛋白，但近期临床研究主要集中在TF表达、肿瘤进展和组织学分级之间的相关性。因此，为探讨TF在结直肠癌血行转移中的作用及潜在机制，作者分析了手术标本中TF表达、肝转移和VEGF基因表达之间的相关性。此外，他们还分析了TF表达对患者总体生存的预后意义。
分别采用免疫组织化学和Northern印迹分析研究了67例晚期结直肠癌标本中TF和VEGF基因的表达。采用单因素和多因素统计学方法分析TF表达、肝转移及其他因素之间的相关性。采用Kaplan-Meier法计算生存率。
单因素和多因素分析显示，TF表达是肝转移的一个显著（P = 0.0001）且独立的危险因素，而TF与VEGF基因表达之间存在微弱但不显著的相关性。在所有病例中（P = 0.0001）以及在无同步肝转移的病例中（P = 0.0156），TF阳性组的预后均明显较差。
尽管确切机制尚不清楚，但TF表达是结直肠癌患者肝转移和预后的一个合适指标。
