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五种常用免疫组化标志物TTF-1、Napsin A、CK7、CK5/6和P63在原发性及转移性肺腺癌和肺鳞状细胞癌中的应用:246例细针穿刺病例的回顾性研究

Utility of five commonly used immunohistochemical markers TTF-1, Napsin A, CK7, CK5/6 and P63 in primary and metastatic adenocarcinoma and squamous cell carcinoma of the lung: a retrospective study of 246 fine needle aspiration cases.

作者信息

Gurda Grzegorz T, Zhang Lei, Wang Yuting, Chen Li, Geddes Susan, Cho William C, Askin Frederic, Gabrielson Edward, Li Qing Kay

机构信息

The Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287 USA.

The Department of Pathology and Division of Cytopathology, University of Chicago Hospitals, Chicago, IL 60637 USA.

出版信息

Clin Transl Med. 2015 Apr 21;4:16. doi: 10.1186/s40169-015-0057-2. eCollection 2015.

Abstract

BACKGROUND

Fine needle aspiration (FNA) biopsy plays a critical role in the diagnosis and staging of lung primary and metastatic lung carcinoma. Accurate subclassification of adenocarcinoma (ADC) and/or squamous cell carcinoma (SqCC) is crucial for the targeted therapy. However, the distinction between ADC and SqCC may be difficult in small FNA specimens. Here, we have retrospectively evaluated the utility of TTF-1, Napsin A, CK7, P63 and CK5/6 immunohistochemical (IHC) markers in the distinguishing and subclassification of ADC and SqCC.

METHODS

A total of 246 FNA cases were identified by a computer search over a two-year period, including 102 primary NSCLC and 144 primary NSCLC which had metastasized to other sites. The immunostaining patterns of TTF-1, Napsin A, CK7, P63 and CK5/6 were correlated with the histological diagnosis of the tumor.

RESULTS

In 72 primary ADCs, TTF-1, Napsin A and CK7 showed a sensitivity and specificity of 84.5%/96.4%, 92.0%/100%, and 93.8%/50.0%. In 30 primary SqCCs, CK5/6 and P63 showed a sensitivity and specificity of 100%/77.8% and 91.7%/78.3%. In 131 metastatic ADCs, Napsin A showed the highest specificity (100%), versus TTF-1 (87.5%) and CK7 (25%) but decreased sensitivity (67.8% versus 86.9% and 100%); whereas in 13 metastatic SqCCs, CK5/6 and P63 showed a sensitivity/specificity of 100%/84.6% and 100%/68.4%. Bootstrap analysis showed that the combination of TTF-1/CK7, TTF-1/Napsin A and TTF-1/CK7/Napsin A had a sensitivity/specificity of 0.960/0.732, 0.858/0.934, 0.972/0.733 for primary lung ADCs and 0.992/0.642, 0.878/0.881, 0.993/0.618 for metastatic lung ADCs.

CONCLUSIONS

Our study demonstrated that IHC markers had variable sensitivity and specificity in the subclassification of primary and metastatic ADC and SqCC. Based on morphological findings, an algorithm with the combination use of markers aided in the subclassification of NSCLCs in difficult cases.

摘要

背景

细针穿刺(FNA)活检在肺原发性和转移性肺癌的诊断及分期中起着关键作用。腺癌(ADC)和/或鳞状细胞癌(SqCC)的准确亚分类对于靶向治疗至关重要。然而,在小的FNA标本中区分ADC和SqCC可能具有挑战性。在此,我们回顾性评估了甲状腺转录因子-1(TTF-1)、天冬氨酸蛋白酶A(Napsin A)、细胞角蛋白7(CK7)、P63和细胞角蛋白5/6(CK5/6)免疫组化(IHC)标志物在ADC和SqCC鉴别及亚分类中的作用。

方法

通过计算机检索在两年期间共识别出246例FNA病例,包括102例原发性非小细胞肺癌(NSCLC)和144例已转移至其他部位的原发性NSCLC。TTF-1、Napsin A、CK7、P63和CK5/6的免疫染色模式与肿瘤的组织学诊断相关。

结果

在72例原发性ADC中,TTF-1、Napsin A和CK7的敏感性和特异性分别为84.5%/96.4%、92.0%/100%和93.8%/50.0%。在30例原发性SqCC中,CK5/6和P63的敏感性和特异性分别为100%/77.8%和91.7%/78.3%。在131例转移性ADC中,Napsin A显示出最高的特异性(100%),而TTF-1为87.5%,CK7为25%,但敏感性降低(分别为67.8%、86.9%和100%);而在13例转移性SqCC中,CK5/6和P63的敏感性/特异性分别为100%/84.6%和100%/68.4%。自抽样分析显示,对于原发性肺ADC,TTF-1/CK7、TTF-1/Napsin A和TTF-1/CK7/Napsin A组合的敏感性/特异性分别为0.960/0.732、0.858/0.934、0.972/0.733;对于转移性肺ADC,分别为0.992/0.642、0.878/0.881、0.993/0.618。

结论

我们的研究表明,IHC标志物在原发性和转移性ADC及SqCC的亚分类中具有不同的敏感性和特异性。基于形态学发现,联合使用标志物的算法有助于在疑难病例中对NSCLC进行亚分类。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7f8/4417108/a583a246e1ab/40169_2015_57_Fig1_HTML.jpg

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