非小细胞肺癌切除组织中常用免疫组织化学指标尚不能预测远期生存

The Current Immunohistochemistry Markers in the Resected Tissues of Non-small Cell Lung Cancer Could Not Predict Prognosis

背景与目的在非小细胞肺癌(non-small cell lung cancer,NSCLC)切除组织中寻找可预测远期生存的免疫组化指标一直备受关注。本研究旨在回顾评价单中心历史上曾选用的免疫组化指标与NSCLC预后之间的关系。方法 2008年-2013年我院单一手术组切除NSCLC 722例,选用的免疫组化指标共12个,在随访良好的前瞻性数据基础上,行单因素生存分析及多因素风险回归模型评价这些指标的表达在NSCLC切除生存中的意义。结果曾选用的12个免疫组化分子分别为:血小板衍生生长因子受体(platelet-derived growth factor receptor,PDGFR)(n=460)、切除修复交叉互补1(excision repair cross complementing 1,ERCC1)(n=461)、表皮生长因子受体(epithelial growth factor receptor,EGFR)(n=460)、人血管内皮生长因子受体3(vascular endothelial growth factor receptor 3,VEGFR3)(n=451)、NM23(n=359)、MRP(n=351)、P170(n=353)、TS(n=431)、Tubulin(n=307)、核糖核苷酸还原酶M1(ribonucleotide reductase M1,RRM1)(n=381)、环氧酶2(cyclooxygenase 2,COX2)(n=364)和TOPII(n=235)。单因素分析显示仅有VEGFR3的表达与生存有关,阳性表达者与阴性表达者的5年生存率分别为77.6%与65.0%(P=0.042)。但多因素分析表明VEGFR3不是NSCLC独立的预后因素。结论本组所选用的免疫组织化学指标不能预测切除后的NSCLC患者的生存。

Background and objective It has been drawn much attention to identify the molecular markers by immunohistochemistry（IHC） for evaluating the prognosis of non-small cell lung cancer（NSCLC） following resection. The aim of this study is to retrospectively associate ever tested IHC markers and prognosis of NSCLC after resection. Methods A total of 722 NSCLC patients underwent surgery by single surgeon team from 2008 to 2013. Twelve molecular markers had been examined by IHC and the staining signals was re-scored with unified standard. Survival analysis by univariate and multivariate was carried out to assess the significance of these markers in prognosis of NSCLC in our prospective database with strict follow-up. Results The following twelve IHC markers had been tested between 2008 and 2013, including platelet-derived growth factor receptor（PDGFR）（n=124）, excision repair cross complementing 1（ERCC1）（n=124）, epithelial growth factor receptor（EGFR）（n=131）, vascular endothelial growth factor receptor 3（VEGFR3）（n=142）, NM23（n=129）, MRP（n=109）, P170（n=104）, TS（n=143）, Tubulin（n=133）, ribonucleotide reductase M1（RRM1）（n=131）, ribonucleotide reductase M1（COX2）（n=138）, and TOPII（n=127）. Only VEGFR3 expression was correlated with prognosis of the patients by univariate analysis, with 5-yrs survival rate being 77.6% and 65.0%（positive vs. negative） respectively（P=0.042）. However, VEGFR3 was not an independent prognostic factor for this series of NSCLC patients in multivariate analysis. Conclusion These twelve IHCmarkers could not predict prognosis of NSCLC patients after surgery in our series.