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余 何, 李 镭, 刘 丹, 等.TTF-1、NapsinA、P63和CK5/6在肺癌组织的表达与分型诊断的价值.四川大学学报(医学版),2017,48(3):336-341
TTF-1、NapsinA、P63和CK5/6在肺癌组织的表达与分型诊断的价值
Expression of TTF-1, NapsinA, P63, CK5/6 in Lung Cancer and Its Diagnostic Values for Histological
  
中文关键词:  TTF-1 NapsinA P63 CK5/6 肺癌 组织学分型
英文关键词:TTF-1 NapsinA P63 CK5/6 Lung cancer Histological classification
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中文摘要:
      目的探讨甲状腺转录因子(TTF-1)、天冬氨酸蛋白酶A(NapsinA)、转录因子P63(P63)和细胞角蛋白5/6(CK5/6)在肺癌组织中的表达,以及在肺癌组织学分型中的诊断价值。方法采用免疫组化染色检测964例肺癌患者癌组织TTF-1(929例)、NapsinA(113例)、P63(282例)、CK5/6(277例)蛋白的表达,分析蛋白表达与肺癌临床病理特征的关系;采用受试者工作特征 (ROC)曲线分析4个因子各自的诊断价值,计算其曲线下面积(AUC),分析其表达阳性时分型诊断的敏感性和特异性。对同时检测了4个因子表达的44例患者行多因素logistic回归分析,检验其判定肺鳞癌/肺腺癌的价值。结果本研究纳入964例肺癌患者,其中腺癌552例,鳞癌146例,小细胞肺癌253例,大细胞肺癌13例;平均年龄56岁,男性占63.4%。TTF-1、NapsinA、P63和CK5/6在肺癌组织中的阳性表达率分别为76.3%(709/929)、67.3%(76/113)、47.2%(133/282)和34.7%(96/277)。TTF-1、NapsinA在腺癌中的阳性表达率高,其表达阳性时诊断肺腺癌的敏感性分别为81.15%、82.05%,特异性分别为30.41%、65.71%,AUC分别为0.557 8( P=0.002 6,95%CI:0.520 0~0.595 6)、0.738 8( P<0.000 1,95%CI:0.633 4~0.844 2)。P63、CK5/6在鳞癌中的阳性表达率高,其表达阳性时诊断肺鳞癌的敏感性分别为80.68%、81.25%,特异性分别为68.04%、84.26%,AUC为0.7436(P<0.000 1,95%CI:0.681 9~0.805 3)、0.827 6(P<0.000 1,95%CI:0.770 0~0.885 2)。小样本(44例肺鳞癌/肺腺癌)多因素回归分析发现,NapsinA阳性可独立诊断肺腺癌(偏回归系数=2.826,P=0.022),而其他指标不具有独立进行肺鳞癌/肺腺癌分型诊断的价值(P>0.05)。结论TTF-1和NapsinA均可作为诊断肺腺癌的生物标志物,P63、CK5/6可作为诊断肺鳞癌的生物标志物。NapsinA阳性可于肺鳞癌/肺腺癌分型诊断中独立诊断肺腺癌。
英文摘要:
      Objective To investigate the expressions of thyroid transcription factor-1(TTF-1), NapsinA, P63 and CK5/6 in lung cancer tissues and their diagnostic value for histological classification. Methods The protein expression in a total of 964 lung cancer samples was detected by immunohistochemistry, of which 929 cases for TTF-1, 113 cases for NapsinA, 282 cases for P63, and 277 for CK5/6, respectively. The correlations between the protein expressions of the four markers and clinicopathological features in lung cancer patients were analyzed. The area under the curves (AUCs) of ROC curves, sensitivity and specificity were calculated to determine the diagnostic values for the four markers. Results There were 552 cases of lung adenocarcinoma (ADC), 146 cases of lung squamous cell carcinoma (SCC), 253 cases of small cell carcinoma (SCLC), and 13 cases of large cell carcinoma (LCC). The median age was 56 years old, and 63.4% was male. The positive expression rates of TTF-1, NapsinA, P63, and CK5/6 were 76.3% (709/929), 67.3% (76/113) , 47.2% (133/282) and 34.7% (96/277), respectively. The positive expression rates of TTF-1 and NapsinA were higher in lung ADC, and the sensitivity and specificity of TTF-1 in the diagnosis of ADC were 81.15% and 30.41% respectively, those of NapsinA were 82.05% and 65.71% respectively. The AUCs for TTF-1 and NapsinA were 0.557 8 (P=0.002 6,95%CI:0.520 0-0.595 6) and 0.738 8 (P<0.000 1,95%CI:0.633 4-0.844 2) respectively. The positive expression rates of P63 and CK5/6 were significantly higher in lung SCC, and their sensitivities to diagnose SCC were 80.68% and
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