VEGF的表达是胰腺癌术后化疗是否有效的重要指标
在ASCO的2005年的胃肠肿瘤座谈会上,Khorana作了“VEGF的表达是术后化疗是否有效的指标”的报告。血管生成是胰腺癌进展的重要过程,VEGF是促进血管生成的重要因子,DPC4是血管生成的抑制因子,Khorana等对128例手术切除的胰腺癌组织进行微阵列分析,发现有术后胰腺癌需要辅助化疗的预后指标有:
1.VEGF表达
2.DPC4缺失
3.高的微血管密度的
有以上任一指标的患者接受术后化疗比不接受有更长的生存期,并且有统计学意义。
该研究有一定的局限性:
1.回顾性研究
2.没有对年龄和性别进行匹配
3.辅助化疗没有标准化
4.对于那些局限表达的病人,低估了其真正的表达率
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VEGF expreion predicts adjuvant therapy outcomes in resected pancreatic cancer
Author(s): A. A. Khorana, C. K. Ryan, Y. C. Hu, R. A. Komorowski, S. A. Ahrendt
Atract: Background: Angiogenesis is important for the progreion of pancreatic cancer, but its predictive &#118alue is not known. We investigated the aociation of various angiogenic factors and microveel deity (MVD) with adjuvant therapy and prognosis in resected pancreatic cancer. Methods: Tiue cores from a multi-ititutional retroective series of 128 resected patients were used to build a pancreatic cancer tiue microarray. Vascular endothelial growth factor (VEGF), platelet-derived endothelial cell growth factor (PD-ECGF), CD31 (for MVD) and DPC4 expreion were determined using immunohistochemistry. Results: Expreion of VEGF and PD-ECGF, both proangiogenic factors, was oerved in 74 (58%) and 75 (59%) tumors, reectively. Expreion of DPC4, an angiogenesis inhibitor, was oerved in 59(46%) tumors. VEGF expreion correlated significantly with increased MVD (p=0.03). Pancreatic cancers with lo of the angiogenesis inhibitor DPC4 also showed increased MVD (p=0.05). However, PD-ECGF expreion did not correlate with MVD. Median survival in patients with VEGF-negative tumors was longer than in those with VEGF-positive tumors (20.2 versus 14.7 month HR 0.71, 95%CI, 0.51-1.12; p=0.16). Use of adjuvant therapy was aociated with increased survival in patients with VEGF-positive tumors (18.9 [treated] versus 11.2 [untreated] month HR 0.38, 95%CI, 0.19-0.76; p=0.005). However, no survival benefit from adjuvant therapy was oerved in patients with VEGF-negative tumors. Conversely, adjuvant therapy was aociated with significantly increased survival in patients with lo of angiogenesis inhibitor DPC4 (20.3 [treated] versus 11.2 [untreated] month HR 0.36, 95%CI, 0.14-0.94; p=0.002), but not in those with normal DPC4 expreion. PD-ECGF expreion and MVD were not aociated with survival. Conclusio: VEGF (stimulator) and DPC4 (inhibitor) are important regulators of pancreatic tumor angiogenesis and predictive of benefit from adjuvant therapy in resected pancreatic cancer. This suggests that adjuvant therapy may be both anti-angiogenic and cytotoxic. Addition of anti-VEGF agents to adjuvant regime may further improve outcomes.