胰腺癌中微血管新生及其生成因子的表达和意义

Intratumor Angiogenesis and Expression of Angiogenic Factors in Human Pancreatic Cancer

目的：以微血管密度（ microvessel density, MVD）及血管内皮生长因子（ vascular endothelial growth factor, VEGF）和碱性纤维生长因子（ basic fibroblast growth factor, bFGF）为指标，探讨微血管新生及 VEGF、 bFGF的表达与胰腺癌生物学行为的相关性和临床意义。方法：采用免疫组化法，分别用抗 FⅧ因子多抗、 VEGF多抗及 bFGF单抗对 47例胰腺癌组织切片进行 MVD的测定，并观察 VEGF及 bFGF蛋白的表达。结果：胰腺癌组织中 MVD (10.32± 3.32)显著高于癌旁正常胰腺组织 (6.72± 1.73)(P< 0.01）。 47例标本中， VEGF阳性表达 27例 (57.44％ )， bFGF阳性表达 30例 (63.82％ )， MVD计数与 VEGF、 bFGF的过度表达呈正相关（ P< 0.05）。 MVD及 bFGF、 VEGF表达与胰腺癌的临床分期呈正相关（ P< 0.05）。癌组织中 MVD高者及 bFGF过度表达者术后存活率较低（ P< 0.05）。结论：瘤内 MVD与胰腺癌的生长、浸润及转移密切相关，并对判断预后有重要临床意义 ;VEGF与 bFGF的过度表达在胰腺癌微血管生成过程中起重要作用，提示两者及其受体可作为抗血管生成以治疗胰腺癌的靶点，或监测疗效的指标。

Objective： This study was designed to investigate microvessel density (MVD) and expression of vascular endothelial growth factor (VEGF)， basic fibroblast growth factor (bFGF) in pancreatic cancer, and the relevance of these three indexes to the biological behavior of the cancer． Methods： Intratumor MVD and the expression of VEGF and bFGF were examined by immunohistochemical staining in 47 pancreatic cancer tissues (polyclonal antibody for FⅧ and VEGF, monoclonal antibody for bFGF), and the relationship between either MVD or the expression of these two angiogenic factors and the clinicopathological features, including survival were analyzed． Results： MVD in cancer tissues was higher (10.32± 3.32) than that in normal tissues (6.72± 1.73) (P< 0.01). In 47 cases, the positive rate of expression of VEGF, bFGF protein in pancreatic cancer was significantly higher than that in normal tissues(P< 0.05), 57.44％ of 47 pancreatic cancer were positive for VEGF protein in cancer cells,and 63.82％ showed strong bFGF staining in cancer and infilbrating cells． The overexpression of VEGF and bFGF protein correlated significantly with high MVD (P< 0.05). Advanced pathological grade of the disease was significantly more frequent in the patients with high MVD, positive staining of VEGF and bFGF, (P< 0.01)． The higher MVD and the overexpression of bFGF correlated with poor survival (P< 0.05)． Conclusions： Intratumor MVD is strongly related to the progress, invasiveness and metastasis of pancreatic cancer, and may serve as a meaningful prognostic factor． The overexpression of VEGF and bFGF may play an important role in the process of tumor-associated neovascularization and suggest that VEGF or bFGF system may be promising target for antiangiongenic strategy of pancreatic cancer．