TCT联合免疫组织化学在NSCLC恶性胸腔积液诊断中的价值

Clinical value of TCT combined with immunohistochemistry in diagnosis of malignant pleural effusion caused by NSCLC

目的采用液基薄层细胞学检查(TCT)与免疫组织化学检测甲状腺转录因子1(TTF-1)、细胞角蛋白7(CK7)、细胞角蛋白5/6(CK5/6)和P63在恶性胸腔积液中的表达,探讨这2种检测方法联合诊断非小细胞肺癌(NSCLC)致恶性胸腔积液及在分型诊断中的临床价值。方法采用TCT对703例胸腔积液进行细胞学涂片,筛选出疑似肿瘤细胞和肿瘤细胞标本281例;再利用免疫组织化学染色对确诊为NSCLC恶性胸腔积液的137例患者进行肺腺癌、鳞癌分型诊断;最后采用ROC曲线计算其曲线下面积,进一步判断该指标是否具有诊断价值。结果初筛703例胸腔积液,137例为NSCLC所致的恶性积液,其中肺腺癌110例、肺鳞癌25例、肺腺鳞癌2例。CK5/6、P63、TTF-1及CK7在肺鳞癌和肺腺癌致恶性胸腔积液标本中的阳性表达率比较,差异有统计学意义(P<0.05)。CK5/6在肺鳞癌所致恶性胸腔积液中敏感性、特异性分别为92.86%(95%CI:0.64,0.99)和89.58%(95%CI:0.77,0.99);P63在肺鳞癌致恶性胸腔积液中敏感性、特异性分别为91.67%(95%CI:0.60,0.99)和72.73%(95%CI:0.54,0.86)。TTF-1在肺腺癌致恶性胸腔积液中的敏感性、特异性分别为87.18%(95%CI:0.77,0.93)和90.63%(95%CI:0.74,0.98);CK7在肺腺癌致恶性胸腔积液中敏感性、特异性分别为94.23%(95%CI:0.83,0.98)和75.00%(95%CI:0.41,0.93)。TTF-1和CK7诊断肺腺癌致恶性胸腔积液的ROC曲线下面积(AUC)分别为0.821和0.774;CK5/6和P63诊断肺鳞癌致恶性胸腔积液的(AUC)分别为0.805和0.755。结论TTF-1和CK7、CK5/6和P63分别对肺腺癌、鳞癌致恶性胸腔积液有重要的诊断价值,TCT联合免疫组织化学对良恶性胸腔积液的鉴别诊断及NSCLC致恶性胸腔积液的分型诊断具有临床应用价值,值得推广应用。

Objective To examine the cytopathology and Thyroid Transcription Factor (TTF-1), Cytokeratin 7 (CK7), Cytokeratin 5/6 (CK5/6) and P63 in the pleural effusion by the Thin-Cytologic Test (TCT) and the immunohistochemistry method, and then to evalue the clinical application of these combined method in diagnosing malignant pleural effusion caused by non-small cell lung cancer (NSCLC) classification diagnosis. Methods Firstly, we screened out 281 cases of suspected tumor cells and tumor cells by the TCT method from 703 pleural effusion cases. Secondly, we tested the TTF-1, CK7, CK5/6 and P63 by the immunohistochemistry method in the 137 cases pleural effusion caused by confirmed NSCLC to classify adenocarcinoma and squamous cell carcinoma. Finally, we calculated the area under the curve (AUC) and evalued the clinical diagnostic value. Results We found 137 malignant effusion cases caused by NSCLC from 703 pleural effusions cases, including 110 cases of lung adenocarcinoma, 25 cases of lung squamous cell carcinoma and 2 cases of lung adenosquamous carcinoma. The positive rates of CK5/6, P63, TTF-1 and CK7 in malignant pleural effusion caused by lung squamous cell carcinoma and lung adenocarcinoma were significantly different (P < 0.05). The sensitivity and specificity of CK5/6 in malignant pleural effusion caused by lung squamous cell carcinoma were 92.86%(95% CI: 0.64, 0.99) and 89.58%(95% CI: 0.77, 0.99);those of P63 were 91.67%(95% CI: 0.60, 0.99) and 72.73%(95% CI: 0.54, 0.86);those of TTF-1 were 87.18%(95% CI: 0.77, 0.93) and 90.63%(95% CI: 0.74, 0.98);those of CK7 were 94.23%(95% CI: 0.83, 0.98) and 75.00%(95% CI: 0.41, 0.93). The AUC of ROC curve for TTF-1 and CK7 in the diagnosis of lung adenocarcinoma were 0.821 and 0.774 respectively;correspondingly, those of the CK5/6 and P63 in the diagnosis of squamous cell carcinoma were 0.805 and 0.755 respectively. Conclusions The TTF-1, CK7, CK5/6, and P63 are important in guiding the diagnosis of lung adenocarcinoma and squamous cell carcinoma. Thin-Cytologic Test combined with the immunohistochemistry method is clinically useful for the pathological diagnosis and classification of malignant effusion caused by NSCLC.