促红细胞生成素及其受体在非小细胞肺癌中的表达及临床意义

Expression and clinical significance of erythropoietin and erythropoietin receptor in non-small cell lung cell

目的研究促红细胞生成素（EPO）及其受体（EPO-R）在非小细胞肺癌（NSCLC）中的表达及临床意义。方法应用免疫组织化学法检测唐山市协和医院、唐山市人民医院1999年1月至2003年12月手术切除的126例NSCLC EPO与EPO-R蛋白的表达,并分析其与临床病理参数的相关性。结果 NSCLC患者中EPO阳性率为59.5%（75/126）,高、中、低分化阳性率分别为27.7%,54.0%,74.1%,低分化者阳性率高于中、高分化者（P〈0.01）;Ⅰ~Ⅱ期阳性率为37.1%,Ⅲ~Ⅳ期为68.1%（P〈0.01）;淋巴结转移者（63.3%）明显高于淋巴结阴性者（35.3%）（P〈0.01）。EPO表达阴性者中位生存期为65个月,EPO表达弱阳性至中度阳性者中位生存期为26个月,EPO强阳性者为10个月（P〈0.01）。NSCLC患者中EPO-R阳性率为78.6%（99/126）。高、中、低分化阳性率分别为38.9%,74.0%,94.8%,低分化和中分化者阳性率明显高于高分化者（P〈0.01）;Ⅰ~Ⅱ期阳性率为40.0%,Ⅲ~Ⅳ期为93.4%（P〈0.01）;淋巴结转移者（80.7%）明显高于淋巴结阴性者（64.7%）（P〈0.01）。EPO-R表达阴性者中位生存期为69个月,EPO-R表达弱阳性至中度阳性者中位生存期为49个月,EPO-R强阳性者为11个月（P〈0.01）。COX回归分析显示,EPO表达（P〈0.01）、EPO-R表达（P〈0.01）均为独立的预后因素。结论 EPO和EPO-R高水平表达与NSCLC侵袭转移相关,EPO和EPO-R高表达与NSCLC预后不良相关。

Objective To investigate the expression pattern and clinical significance of erythropoietin（EPO）/erythropoietin receptor（EPO-R） in non-small cell lung cancer（NSCLC）.Methods EPO and EPO-R protein expression were assessed by immunohistochemistry in samples obtained from 126 patients with NSCLC from January 1999 to December 2003,then potential correlations of EPO and EPO-R immunostaining and clinicopathologic features were analyzed.Results EPO immunostaining was seen in 75 of 126 NSCLC samples（59.5%）.EPO immunostaining in well-differentiated,moderately differentiated and poor differentiated samples was 27.7%,54.0% and 74.1% respectively,and their difference had statistic difference（P0.01）.The expression of EPO was remarkably higher in stage Ⅲ-Ⅳ than in stageⅠ-Ⅱ,68.1% vs 37.1%（P0.01）.The expression of EPO was much higher in patients with lymph node metastasis than that of negative lymph node,63.3% vs 35.3%（P0.01）.Median overall survival of patients with negative EPO was 65 months,while weak-medium positive immunostaining 26 months,strong immunostaining 10 months（P0.01）.EPO-R immunostaining was observed in 99 of 126 NSCLC samples（78.6%）.EPO-R immunostaining in well-differentiated,moderately differentiated and poor differentiated samples was 38.9%,74.0% and 94.8%,respectively,and their difference was noticeable（P0.01）.The expression of EPO-R was much higher in stage Ⅲ-Ⅳ than in stageⅠ-Ⅱ,93.4% vs 40.0%（P0.01）.The expression of EPO-R was remarkably higher in patients with lymph node metastasis than that of negative lymph node,80.7% vs 64.7%（P0.01）.Median overall survival of patients with negative EPO-R was 69 months,while week-medium positive immunostaining 49 months,strong immunostaining 11 months（P0.01）.Multivariate COX proportional hazard models showed EPO expression（P0.01） and EPO-R expression（P0.01） were independent prognostic factors.Conclusion High level expressions of EPO and EPO-R were notably associated with NSCLC invasiveness and metastasis.High expressions of EPO and EPO-R were significantly correlated with poor prognosis in patients with NSCLC.