Nishino Michiya, Hoang Mai P, Della Pelle Patricia, Morales-Oyarvide Vicente, Huynh Tiffany G, Mark Eugene J, Mino-Kenudson Mari
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
Cancer Cytopathol. 2016 Jul;124(7):472-84. doi: 10.1002/cncy.21707. Epub 2016 Feb 29.
Subtyping non-small cell lung carcinomas (NSCLC) into adenocarcinoma (ACA) or squamous cell carcinoma (SQCC) is important for treatment and specimen triage for molecular studies. To preserve tissue for molecular studies in cytology/small biopsy specimens, a 2-antibody cocktail for NSCLC subtyping was developed.
Markers for lung ACA (thyroid transcription factor 1 and napsin A) and SQCC (cytokeratin 5/6 and p40) were evaluated on tissue microarrays (TMAs) with 143 ACA and 98 SQCC specimens. The napsin A/p40 combination was selected for NSCLC subtyping and validated on the TMA as well as on a cohort of cell block/small biopsy specimens from 80 poorly differentiated NSCLCs.
Using TMA analysis, the napsin A-positive (+)/p40± immunophenotype identified ACA with 94% sensitivity and 100% specificity, whereas the napsin A (negative)-/p40+ immunophenotype identified SQCC with 100% sensitivity and specificity. On the validation cohort of 80 cell block and small biopsy specimens, the napsin A/p40 cocktail accurately subtyped 63 of 70 NSCLC (90%) as ACA or SQCC using the subsequent surgical resection as reference histology. Of the remaining 17 cases, 15 were classified as NSCLC-not otherwise specified based on a napsin A-/p40- immunophenotype; their corresponding resections were diagnosed as ACA (7 cases), large cell carcinoma (7 cases), or pleomorphic carcinoma (1 case). Two additional large cell carcinoma cases showed a napsin A-/p40+ or napsin A+/p40+ profile in the preoperative cell block/small biopsy sample.
A napsin A/p40 cocktail can accurately subtype NSCLC into ACA and SQCC in most cell block/small biopsy specimens of poorly differentiated NSCLC. In the minority of cases in which the napsin A/p40 immunophenotype is indeterminate, additional stains may be necessary for precise classification. Cancer Cytopathol 2016;124:472-84. © 2016 American Cancer Society.
将非小细胞肺癌（NSCLC）分为腺癌（ACA）或鳞状细胞癌（SQCC）对于治疗及分子研究的标本分类而言至关重要。为了在细胞学/小活检标本中保存用于分子研究的组织，研发了一种用于NSCLC分型的双抗体鸡尾酒法。
在含有143例ACA和98例SQCC标本的组织微阵列（TMA）上评估肺ACA（甲状腺转录因子1和 napsin A）和SQCC（细胞角蛋白5/6和p40）的标志物。选择napsin A/p40组合用于NSCLC分型，并在TMA以及来自80例低分化NSCLC的细胞块/小活检标本队列中进行验证。
通过TMA分析，napsin A阳性（+）/p40±免疫表型识别ACA的灵敏度为94%，特异性为100%，而napsin A阴性（-）/p40+免疫表型识别SQCC的灵敏度和特异性均为100%。在80例细胞块和小活检标本的验证队列中，以后续手术切除标本的组织学检查结果作为参考，napsin A/p40鸡尾酒法将70例NSCLC中的63例（90%）准确地分为ACA或SQCC。其余17例中，15例基于napsin A-/p40-免疫表型被分类为非特指NSCLC；其相应的手术切除标本被诊断为ACA（7例）、大细胞癌（7例）或多形性癌（1例）。另外2例大细胞癌病例在术前细胞块/小活检样本中显示为napsin A-/p40+或napsin A+/p40+特征。
在大多数低分化NSCLC的细胞块/小活检标本中，napsin A/p40鸡尾酒法可准确地将NSCLC分为ACA和SQCC。在少数napsin A/p40免疫表型不确定的病例中，可能需要额外的染色以进行精确分类。《癌症细胞病理学》2016年；124:472 - 84。©2016美国癌症协会
