联合检测EGFR、CEA对恶性胸腔积液的诊断价值

The diagnostic value of combined detection of EGFR and CEA for malignant pleural effusion

目的:评价联合检测胸腔积液患者的胸水细胞块表皮生长因子受体(epidermal growth factor receptor,EGFR)基因拷贝数,以及胸水、血清CEA水平对良恶性胸腔积液鉴别诊断的价值。方法:应用荧光原位杂交技术(Fish法)检测恶性胸腔积液(n=35)、良性胸腔积液(n=30)组患者胸水细胞块EGFR基因拷贝数水平。采用电化学发光全自动生化分析仪检测胸水及血清中CEA水平,根据受试者工作特性曲线(ROC)选取最佳灵敏性和特异性的点作为临界值,评价CEA及联合检测EGFR基因拷贝数对良恶性胸腔积液的诊断价值。结果:35例恶性胸腔积液完成Fish检测。恶性胸腔积液中15例阴性,20例阳性,阳性率为57.1%。其中13例为EGFR基因高度多体性,7例为EGFR基因扩增。肺腺癌16例中,EGFR基因高度多体性、扩增14例,肺腺癌扩增率为87.5%;肺鳞癌14例中,EGFR基因簇状扩增3例(21.4%),点状扩增3例(21.4%),无扩增8例(57.1%),肺鳞癌扩增率为42.9%。腺癌Fish阳性率(87.5%)高于鳞癌(42.9%),P<0.01。30例良性胸腔积液中有1例脓胸患者EGFR Fish检测阳性,阳性率为3.3%,余检测结果均阴性。恶性胸腔积液患者胸水及血清CEA分别为(220.9±71.65)ng/ml、(18.11±11.38)ng/ml,显著高于良性胸腔积液组(2.31±1.29)ng/ml、(1.67±1.06)ng/ml,差异有统计学意义(P<0.01)。其中,恶性胸腔积液胸水CEA明显高于血清CEA,而良性胸腔积液组中,胸水CEA与血清CEA无明显差异。肺腺癌所致胸水及血清CEA分别为(441.02±102.65)ng/ml、(32.87±28.66)ng/ml,鳞癌所致胸水及血清CEA分别为(28.75±21.39)ng/ml、(5.99±5.32)ng/ml,腺癌显著高于鳞癌,差异有统计学意义(P<0.01)。比较胸水EGFR、CEA对良恶性胸腔积液诊断的效能,两者之间无明显差异(P=0.453>0.05)。Spearman相关性分析胸水EGFR同CEA之间存在显著正相关。结论:EGFR在恶性胸腔积液的形成中起重要作用,通过Fish技术检测胸水细胞块EGFR基因拷贝数可行,其敏感性为57.1%。对肺腺癌导致恶性胸腔积液的诊断敏感性为87.5%。CEA(临界值5.0ng/ml)在恶性胸腔积液及血清中显著高于良性,其中胸水CEA检测诊断敏感性为65.7%,而在腺癌中为87.5%,其在胸水及血清中的比值>1.5有助于恶性胸腔积液的诊断。EGFR基因突变阳性与肿瘤标记物CEA阳性表达呈正相关,尤见于肺腺癌患者,两者联合检测可提高诊断性试验的准确性。

Objective：To evaluate the diagnostic value of combined detection of EGFR and CEA for pleural effu- sion. Methods ： Fluorescence in situ hybridization was used to detect malignant pleural effusion （ n =35 ）, benign pleural effusion （ n = 30）, EGFR gene copy number level, electrochemiluminescence for serum CEA. Results ： 35 cases of malignant pleural effusion complete Fish detection of malignant pleural effusion 15 cases were negative, 20 were positive the positive rate was 57.14%. EGFR gene in 13 cases of multi - body height. Squamous cell carcinoma of the lung ,EGFR gene amplification tufted in three cases （21.4%） ,point like amplified in three cases （21.4%）, no am- plification 8 cases （57.1%） ,lung squamous cell amplification was 42.85%. FISH - positive rate of adenocarcinoma was 87.5% than in squamous cell carcinoma （42.9% ,P 〈 0.01 ） ,30 patients with benign pleural effusion in one case empyema patients with EGFR Fish detect positive rate was 3.33%. Patients with malignant pleural effusion CEA was （ 220.9 ＋ 71.65 ） ng/ml, （ 18. 1 1 ＋ 1 1.38 ） ng/ml, significantly higher than in benign pleural effusion group （2.31 ＋ 1.29） ng/ml ^（ 1.67 ＋ 1.06 ） ng/ml （ P 〈 0.01 ）. Conclusion ： EGFR plays important role in detecting pleural effusion, cell block EGFR gene copy number by Fish viable technology, the sensitivity was 57.1%. For lung cancer and malignant pleural effusion diagnostic sensitivity was 87.5%. CEA （ critical value 5.0ng/ml） in malignant pleural fluid and serum was significantly higher than benign pleural fluid CEA in which the diagnostic sensitivity was 65.7% ,while 87.5% in adenocarcinoma. CEA positive expression of EGFR mutation - positive tumor markers were positively correlated, especially seen in patients with lung cancer, combined detection can improve the accuracy of di-agnosis.