Utility of a Novel Triple Marker (Combination of TTF-1, Napsin-A and P40) in the Subclassification of Non-Small Cell Lung Carcinomas using Fine Needle Aspiration Cases

Summary Personalized treatment of lung cancer requires an accurate subclassification of non-small cell lung carcinoma (NSCLC) into adenocarcinoma (ADC), squamous cell carcinoma (SqCC) and other subtypes. In poorly differentiated tumors especially on small fine needle aspirate (FNA) specimens the subclassification could be difficult in certain cases. Our previous study using resected tumor tissue has shown that the combination of commonly used individual markers (TTF-1, P40 and Napsin A) into a novel triple marker has high sensitivity and specificity in subclassification of NSCLC, and also the advantage of using minimal tumor tissue. In this study, we further evaluated the utility of this novel triple marker using FNA cases. We included primary NSCLC, consisting of 37 SqCCs (primary = 35 and metastasis = 2) and 50 ADCs (primary = 29 and metastasis = 21), 12 metastatic ADCs of non-pulmonary primary, and 10 small cell lung carcinomas (SCLCs). The IHC patterns were semi-quantitatively scored. In lung SqCCs and ADCs, the sensitivity and specificity of the triple marker were 100% and 97.1%, and 86.0% and 100%, respectively. The triple marker showed no immunoreactivity in 12 metastatic non-pulmonary ADCs. In 10 SCLCs, TTF-1 had focal positivity in 40% cases. The limitations of the triple marker include staining of alveolar macrophages (by TTF-1 and Napsin A), basal layer of bronchial epithelial cells (by P40), and non-specific cytoplasmic staining of TTF-1. Our study not only supports our previous finding using resected tumor specimens, but also provides evidence that the triple marker can be used for cytological material, and preserving tumor tissue for molecular testing.