非小细胞肺癌组织MET和EGFR基因扩增与预后相关性分析

Correlation of MET and EGFR amplification with prognosis in non-small cell lung cancer

目的:探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)患者中肝细胞生长因子受体(MET)基因和表皮生长因子受体(epidermal growth factor receptor,EGFR)基因扩增与临床病理特征及预后的关系。方法:回顾分析唐山市协和医院(48例)和唐山市人民医院(109例)2001-01-2007-01手术切除的NSCLC石蜡包埋标本157例。应用荧光原位杂交(fluorescence in situ hybridization,FISH)检测NSCLC MET、EGFR基因扩增情况,并结合临床病理资料进行统计分析。应用SPSS 16.0进行统计分析,Kaplan-Meier模型分析中位生存期(overall survival,OS),Log-rank检验比较生存曲线,多因素分析采用Cox回归模型。结果:157例NSCLC患者标本中,EGFR基因扩增70例(44.6%)。EGFR基因扩增与年龄、性别、吸烟状态、组织类型和TNM分期无关,P>0.05。157例NSCLC患者标本中,MET基因扩增25例(15.9%)。EGFR扩增患者MET扩增率为22.9%,高于无EGFR扩增患者MET扩增率10.3%,P=0.033。MET基因扩增与年龄、性别、吸烟状态、组织类型和TNM分期无关,P>0.05。Kaplan-Meier生存分析显示,Ⅰ+Ⅱ期中位生存期为51个月,明显高于Ⅲ+Ⅳ期中位生存期29个月,P=0.001。EGFR FISH阳性患者中位OS为33个月与EGFR FISH阴性患者中位OS 39个月比较,差异无统计学意义,P=0.495。MET FISH阳性患者中位OS为29个月,低于MET FISH阴性患者37个月,P=0.044。患者OS与病理类型、年龄、性别和吸烟状态无相关性,P>0.05。多因素分析显示,临床分期、MET基因扩增与OS有关(相对危险度为12.573、6.892,P值分别为0.015、0.018)。结论:临床Ⅲ+Ⅳ期和MET基因扩增NSCLC患者预后不良,EGFR基因扩增与NSCLC患者预后无关。

OBJECTIVE：To investigate the relationship between hepatocyte growth factor receptor （MET）,epider- real growth factor receptor （EGFR） amplification and the prognosis in non-small cell lung cancer （NSCLC）. METHODS： Totally 157 cases of formalin-fixed and paraffin-embedded NSCLC tissue specimen surgically removed at Tangshan Xiehe Hospital （48 cases） and Tangshan People＇s Hospital （109 cases） during the period from January,2001 to January,2007 were retrospectively reviewed. Amplification status of EGFR and MET gene were detected by fluorescence in situ hybrid- ization （FISH）,followed by subsequent clinicopathological correlative studies. All analyses were conducted using SPSS version 16.0. The Kaplan-Meier method was used to estimate median overall survival （OS） and the Log-rank test to com- pare survival curves,Cox regression model was used for multivariate analyses. RESULTS：EGFR FISH results were ob tained in 157 cases. EGFR FISH-positive signals （EGFR gene amplification） were observed in 70 cases （44.6%）. There was no significant difference between EGFR FISH-positivity and age, gender, smoking status, histological type, and TNM stage （P〉0.05）. Among 157 NSCLC patients,MET FISH-positive signals（MET gene amplification） was observed in 25 cases （15.9%）. MET status was associated with EGFR amplification （P= 0. 033）. There was no significant differ ence between MET amplification and age, gender, smoking status, histological type, and TNM stage （P〉 0.05）. Median OS of patients in stages Ⅰ --Ⅱ was significantly longer than that in stages Ⅲ - Ⅳ （51 months vs 29 months） （P= 0. 001）. EGFR FISH-positive patients didnt have a significantly shorter median OS than that of EGFR FISH-negative patients （33 months vs 39 months） （P=0. 495）,but MET FISH-positive patients had a significantly shorter median OS than that of MET FISH-negative patients （29 months vs 37 months）（P=O. 044）. There was no remarkable correlation between OS and histological type,age, gender, and smoking status （P〉0.05）. The multivariate analysis showed that the clinical stage, MET gene ampification were significant prognostic factors （RR were 12. 573 and 6. 892, P were 0. 015 and 0. 018）. CONCLUSION：Clinical stage Ⅲ＋Ⅳ and MET gene amplification in NSCLC is closely correlated with poor prog- nosis,but EGFR gene amplification may be not associated with survival in NSCLC patients.