直肠癌组织uPA系统和VEGF表达与浸润转移的关系

Expression of urokinase-type plasminogen activator system and vascular endothelial growth factor in rectal cancer and its correlation with invasion and metastasis

目的研究尿激酶型纤溶酶原激活系统uPA,uPAR,PAI-1蛋白及血管内皮生长因子(VEGF)在直肠癌组织中的表达及其与直肠癌癌生物学行为的关系。方法2005年1月至2006年1月,采用免疫组化S-P法检测67例直肠癌及癌旁组织中uPA,uPAR,PAI-1及VEGF蛋白表达情况,同时对临床病理学资料进行回顾性分析。结果癌和癌周比较uPA,uPAR,PAI-1及VEGF蛋白阳性表达率明显升高(P<0.01),阳性产物主要分布在癌细胞胞质。侵及浆膜组阳性率明显高于未及浆膜组(P=0.000,0.014,0.016,0.000)。uPA,uPAR蛋白在淋巴结转移组中的阳性率明显高于无淋巴结转移组(P=0.002,0.008)。PAI-1蛋白在低分化组中的阳性率明显低于中分化和高分化组(P<0.05)。uPA,uPAR及VEGF蛋白阳性率在直肠癌组织不同分化程度间差异无显著性。在直肠癌组织中uPA,uPAR蛋白的表达呈显著正相关(r=0.653,P<0.001)。在uPA,uPAR蛋白同时阳性的41例病例中,有28例发生淋巴结转移,与阴性组(4/15)相比,转移发生率明显增高(P<0.01)。直肠癌组织中uPA蛋白表达与VEGF表达显著正相关(r=0.300,P<0.05)。PAI-1蛋白表达与VEGF表达具有极显著正相关性(r=0.413,P<0.01)。应用COX回归模型进行多变量分析并采用向前逐步回归法,仅浸润深度、uPA表达和病理类型对淋巴结转移有影响。结论uPA,uPAR,PAI-1及VEGF蛋白在直肠癌组织中表达增强,uPA,uPAR与直肠癌浸润转移密切相关。

Objective To detect the expression of urokinase-type plasminogen activator （uPA） , uPA receptor （uPAR）, plasminogen activator inhibitor type 1 （PAI-1） and vascular endothelial growth factor （VEGF） in rectal cancer （RC） and to reveal their correlation to the major clinicopathological characteristics in- cluding tumor invasion and metastasis. Methods Expression of uPA, uPAR, PAI-1 and VEGF was examined in the tissue sections from 67 cases of RC using streptoavidin-biotin-peroxidase immunohistoehemistry method. Re- sults The expression of uPA, uPAR, PAI-1 and VEGF was mainly located in the cytoplasm of RC cells. The expression of uPA, uPAR, PAI-1 and VEGF in RC was significantly higher than in the cancer-adjacent tissue （ P 〈 0. O1 ）. The expression of uPA, uPAR, PAI-1 and VEGF in RC with serosa invasion was significantly higher than that in cancer without serosa invasion （ P 〈 0. 05 ）. Positive rates of staining for uPA and uPAR in GC with lymph node metastasis were significantly higher compared to cancer without lymph node metastasis （P = 0. 002 and 0. 008 respectively）. The expression of PAI-I was significantly associated with the differentiation degree of cancer （ P 〈 0. 01 ） , while no relationship was found between the expression of uPA, uPAR, VEGF and the differentiation degree of cancer. The expression of uPA was correlated with uPAR in cancer tissue （ r = 0. 653, P 〈 0. 001 ）. In 41 cases positive for uPA and uPAR ,28 were with lymph node metastasis （P 〈0. 01, compared with 4/15）. Positive correlation was observed between the expression of uPA and VEGF protein （r = 0, 300, P 〈 0. 05 ） , and between PAI-1 and VEGF （ r = 0. 413, P 〈 0. 01 ）. Multivariate Cox regression analysis indicated that only the depth of invasion, the expression of uPA and the differentiation affected lymph node metastasis in RC. Conclusion Expression of uPA,uPAR,PAI-1 and VEGF protein is increased in RC. uPA and uPAR may play an important role in the invasion and metastasis through VEGF which promotes angiogenesis.