Caine Graham J, Lip Gregory, Zanetto Ulyses, Maheshwari Mahwandra, Stonelake Paul S, Blann Andrew D
Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, United Kingdom.
Appl Immunohistochem Mol Morphol. 2007 Dec;15(4):382-8. doi: 10.1097/01.pai.0000213137.01536.ca.
Over-expression of angiogenic growth factors and their receptors, and high levels of these molecules in the blood, are a common feature of cancer although the relationships between cell expression and plasma levels are unknown. We hypothesized a significant correlation between the expression and cellular distribution of vascular endothelial growth factor (VEGF), its receptor Flt-1, and the angiopoietin receptor Tie-2 with levels of these molecules in the plasma.
The tissue expression of VEGF, Flt-1, and Tie-2 were investigated by immunohistochemistry, and plasma levels assessed by enzyme-linked immunosorbent assay in 36 patients with breast cancer and 15 with benign breast disease.
Despite expected significant differences in plasma levels of the molecules (P<0.03 to <0.001), no significant differences were found in Tie-2, VEGF, and Flt-1 tissue expression between breast cancer and benign disease controls. No significant correlations were observed between plasma levels of their tissue expression.
Tissue expression of Tie-2, VEGF, and Flt-1 may not be an overly sensitive tool for assessing abnormalities of coagulation, platelet activation, and angiogenesis in human cancer. Plasma markers may not be representative of tumor activity, and may not come wholly from tumor cells. Instead these markers may be indicative of endothelial dysfunction in cancer patients.
血管生成生长因子及其受体的过度表达以及血液中这些分子的高水平是癌症的常见特征,尽管细胞表达与血浆水平之间的关系尚不清楚。我们推测血管内皮生长因子(VEGF)、其受体Flt-1和血管生成素受体Tie-2的表达及细胞分布与血浆中这些分子的水平之间存在显著相关性。
采用免疫组织化学法研究36例乳腺癌患者和15例乳腺良性疾病患者的VEGF、Flt-1和Tie-2的组织表达,并通过酶联免疫吸附测定法评估血浆水平。
尽管这些分子的血浆水平存在预期的显著差异(P<0.03至<0.001),但乳腺癌与良性疾病对照组之间的Tie-2、VEGF和Flt-1组织表达未发现显著差异。其组织表达的血浆水平之间未观察到显著相关性。
Tie-2、VEGF和Flt-1的组织表达可能不是评估人类癌症中凝血、血小板活化和血管生成异常的过于敏感的工具。血浆标志物可能不代表肿瘤活性,也可能并非完全来自肿瘤细胞。相反,这些标志物可能表明癌症患者存在内皮功能障碍。