血管生成及血管浸润与Ⅰ期非小细胞肺癌的预后分层

Prognostic significance of angiogenesis and blood vessel invasion in stage Ⅰ non-small cell lung cancer after complete surgical resection

背景与目的最新的研究发现Ⅰ期非小细胞肺癌(NSCLC)术后辅助化疗可提高患者生存率,因此通过预后分层筛选高危患者给予辅助治疗,既可改善Ⅰ期NSCLC患者的整体预后,又可避免因过度治疗对低危患者造成损害,是目前临床急需解决的问题。本研究旨在探讨肿瘤血管生成和血管浸润(BVI)对Ⅰ期NSCLC预后的影响,建立Ⅰ期NSCLC预后模型。方法回顾性分析118例Ⅰ期NSCLC手术患者的临床病理资料,免疫组织化学检测血管内皮生长因子(VEGF)的表达水平,计算肿瘤内微血管密度(MVD)。以CD34标记的血管腔内瘤细胞的存在判定为BVI。结果肺癌组织VEGF低表达44例(37.3%),高表达74例(62.7%)。VEGF高表达组MVD显著高于低表达组(33.4±17.8vs24.7±14.8,P=0.010),VEGF与MVD间存在正相关(r=0.216,P=0.019)。VEGF高表达患者5年生存率显著低于低表达者(36.48% vs 72.20%,P=0.003)。无BVI者86例(72.9%),BVI者32例(27.1%),后者5年生存率显著低于前者(34.38% vs 60.47%,P=0.018)。多因素分析结果表明VEGF高表达(RR=2.96,P=0.001)和BVI(RR=1.95,P=0.020)为Ⅰ期NSCLC的独立预后因素。进一步根据VEGF表达及BVI情况,将患者分为低度危险组:VEGF低表达+BVI(-);中度危险组:VEGF高表达或BVI(+);高度危险组:VEGF高表达+BVI(+)。三组间5年生存率差异有统计学意义(72.28% vs 52.63% vs 28.00%,P=0.001)。结论VEGF表达与BVI的联合检测可能实现对Ⅰ期NSCLC进行预后分层,为术后患者的个性化治疗提供依据。

Background and objective The latest studies have demonstrated that postoperative adjuvant chemotherapy may improve survival in patients with stage Ⅰ non-small cell lung cancer （NSCLC）, so it was a challenge for clinician to choose the patients who might benefit from adjuvant chemotherapy. The aim of this study is to evaluate the prognostic implications of angiogenesis and tumor blood vessel invasion （BVI） in stage I NSCLC patients who underwent complete resection. Methods One hundred and eighteen stage Ⅰ NSCLC patients undergoing complete resection from 1994-2002 were retrospectively reviewed. Angiogenesis was assessed by vascular endothelial growth factor （VEGF） and mierovessel density （MVD）, BVI was assessed by examining the direct invasion of tumor cells marked by CD34 within vessel lumen. Results Low VEGF expression was seen in 44 patients （37.3%）, high VEGF expression was in 74 patients （62.7%）. The MVD of high VEGF expression cases was much higher than that of low VEGF expression ones （33.4±17.8 vs 24.7± 14.8, P=0. 010）. There was a positive correlation between VEGF and MVD （r=0. 216, P=0. 019）. The 5-year survival rate in patients with high VEGF expression was much lower than in those with low VEGF expression （36.48% vs 72.20%, P=0. 003）. The BVI was present in 32 patients （27.1%） and absent in 86 patients （72.9%）. The 5-year survival rate in patients with presence of BVI was much lower than those with absence of BVI （34. 38% vs 60. 47%, P = 0. 018）. Multivariate COX regression analysis showed that high VEGF expression and BVI were significantly independent predictive factors for overall survival. Finally, the presence of both risk factors, BVI and high VEGF expression was highly predictive of poor outcome （P= 0. 001）. Conclusion Tumor vessel invasion and high VEGF expression are independent prognostic factors for overall survival of postoperative stage Ⅰ NSCLC. The assessment of these factors may improve prognostic stratification for adjuvant therapy or a targeted and specific treatment in stage Ⅰ NSCLC.