经支气管镜针吸活检联合多标志物检测在肺癌病理分型中的应用价值
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摘要
目的评价甲状腺转录因子-1 (TTF-1)、p63、细胞角蛋白(CK) 5、CK7等指标单独或联合应用在肺癌病理分型中的诊断价值。方法通过经支气管镜针吸活检术获得肺癌病理组织标本,采用实时PCR法检测TTF-1、p63、CK5、CK7等标志物的表达水平。结果与肺腺癌相比,肺鳞状细胞癌中TTF-1 (P=0.006)、CK7 (P=0.012)表达水平显著降低,p63 (P=0.008)、CK5 (P=0.025)表达水平显著升高。综合各指标建立综合评分诊断模型,计算综合评分(TS)。TS诊断腺癌和鳞状细胞癌分型时,与各单个指标相比,具有最高的灵敏度(0.942)和特异度(0.841),诊断价值最佳。而与单因素指标相比,TS的腺癌检出率(P=0.040)、鳞状细胞癌检出率(P=0.013)及总检出率(P <0.001)均显著升高。结论利用经支气管镜针吸活检术获取肺癌患者病理组织,并应用实时PCR法检测肺癌分型重要分子标志物TTF-1、p63、CK7、CK5等的表达水平,能够对肺癌病理分型进行诊断分析,且综合运用各分子标志物的TS能够获得更高的诊断效率。
Objective To evaluate the utility of thyroid transcription factor-1(TTF-1),p63,cytokeratin(CK) 5,and CK7 alone or in combination for the pathological typing of lung cancer. Methods The expression of TTF-1,p63,CK5,and CK7 in lung tissue specimens obtained from transbronchial needle aspiration(TBNA) was detected by real-time PCR. Results Compared with that in lung adenocarcinoma,the expression of TTF-1(P = 0.006) and CK7(P = 0.012) in lung squamous cell carcinoma decreased significantly,while that of p63(P = 0.008) and CK5(P = 0.025) increased significantly. Total score(TS) was used to establish a diagnostic model by combining all the markers. TS had the highest sensitivity(0.942) and specificity(0.841) among all single markers used in the pathological typing,as well as the best diagnostic value. Compared with a single marker,the diagnostic performance of TS in adenocarcinoma(P = 0.040) and squamous cell carcinoma(P = 0.013) and total detection rate(P < 0.001) were significantly better. Conclusion Detection of the expression of important molecular markers including TTF-1,p63,CK7,and CK5 by real-time PCR in lung tissue specimens obtained by TBNA is a feasible diagnostic method for the pathological typing of lung cancer. The comprehensive use of various molecular markers can yield higher diagnostic efficiency.
Objective To evaluate the utility of thyroid transcription factor-1(TTF-1),p63,cytokeratin(CK) 5,and CK7 alone or in combination for the pathological typing of lung cancer. Methods The expression of TTF-1,p63,CK5,and CK7 in lung tissue specimens obtained from transbronchial needle aspiration(TBNA) was detected by real-time PCR. Results Compared with that in lung adenocarcinoma,the expression of TTF-1(P = 0.006) and CK7(P = 0.012) in lung squamous cell carcinoma decreased significantly,while that of p63(P = 0.008) and CK5(P = 0.025) increased significantly. Total score(TS) was used to establish a diagnostic model by combining all the markers. TS had the highest sensitivity(0.942) and specificity(0.841) among all single markers used in the pathological typing,as well as the best diagnostic value. Compared with a single marker,the diagnostic performance of TS in adenocarcinoma(P = 0.040) and squamous cell carcinoma(P = 0.013) and total detection rate(P < 0.001) were significantly better. Conclusion Detection of the expression of important molecular markers including TTF-1,p63,CK7,and CK5 by real-time PCR in lung tissue specimens obtained by TBNA is a feasible diagnostic method for the pathological typing of lung cancer. The comprehensive use of various molecular markers can yield higher diagnostic efficiency.
引文
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[9]HERBST RS,O’NEILL VJ,FEHRENBACHER L,et al.PhaseⅡstudy of efficacy and safety of bevacizumab in combination with chemotherapy or erlotinib compared with chemotherapy alone for treatment of recurrent or refractory non-small cell lung cancer[J].J Clin Oncol,2007,25(30):4743-4750.DOI:10.1200/JCO.2007.12.3026.
[10]刘晓骏,张宏宾,吴斌.实时荧光定量PCR在预防性健康体检沙门菌快速筛查中的应用效果[J].江苏预防医学,2018,29(5):546-548.DOI:10.13668/j.issn.1006-9070.2018.05.027.
[2]2015美国国家综合癌症网络(NCCN)指南:肺癌的全身治疗[J].中国全科医学,2015,18(18):2126.
[3]支修益,吴一龙,马胜林,等.原发性肺癌诊疗规范(2011年版)[J].中国肺癌杂志,2012,15(12):677-688.DOI:10.3779/j.issn.1009-3419.2012.12.01.
[4]TRAVIS WD,BRAMBILLA E,RIELY GJ.New pathologic classification of lung cancer:relevance for clinical practice and clinical trials[J].J Clin Oncol,2013,31(8):992-1001.DOI:10.1200/JCO.2012.46.9270.
[5]LOSADA A,TOVAR JA,XIA HM,et al.Down-regulation of thyroid transcription factor-1 gene expression in fetal lung hypoplasia is restored by glucocorticoids[J].Endocrinology,2000,141(6):2166-2173.DOI:10.1210/endo.141.6.7522.
[6]AU NH,GOWN AM,CHEANG M,et al.P63 expression in lung carcinoma:a tissue microarray study of 408 cases[J].Appl Immunohistochem Mol Morphol,2004,12(3):240-247.DOI:10.1097/00129039-200409000-00010.
[7]DOWNEY P,CUMMINS R,MORAN M,et al.If it’s not CK5/6 positive,TTF-1 negative it’s not a squamous cell carcinoma of lung[J].APMIS,2008,116(6):526-529.DOI:10.1007/s11003-008-9005-2.
[8]CHHIENG DC,CANGIARELLA JF,ZAKOWSKI MF,et al.Use of thyroid transcription factor 1,PE-10,and cytokeratins 7 and 20 in discriminating between primary lung carcinomas and metastatic lesions in fine-needle aspiration biopsy specimens[J].Cancer,2001,93(5):330-336.DOI:10.1002/cncr.9048.
[9]HERBST RS,O’NEILL VJ,FEHRENBACHER L,et al.PhaseⅡstudy of efficacy and safety of bevacizumab in combination with chemotherapy or erlotinib compared with chemotherapy alone for treatment of recurrent or refractory non-small cell lung cancer[J].J Clin Oncol,2007,25(30):4743-4750.DOI:10.1200/JCO.2007.12.3026.
[10]刘晓骏,张宏宾,吴斌.实时荧光定量PCR在预防性健康体检沙门菌快速筛查中的应用效果[J].江苏预防医学,2018,29(5):546-548.DOI:10.13668/j.issn.1006-9070.2018.05.027.