ΔNp63, CK5/6, TTF-1 and napsin A, a reliable panel to subtype non-small cell lung cancer in biopsy specimens

Histopathological subtyping of nonsmall cell lung cancer (NSCLC) is currently important in selecting specific therapeutic agents. It can be challenging in distinguishing poorly differentiated lung adenocarcinoma (AC) from squamous cell carcinoma (SCC) on small biopsy samples. This study was aimed to evaluate the utility of a panel of immunohistochemical markers consisting of ΔNp63 (p40), cytokeratins (CK) 5/6, thyroid transcription factor-1 (TTF-1) and napsin A (novel aspartic proteinase of the pepsin family) in subtyping poorly differentiated NSCLC. Forty-eight cases of NSCLC that could not be further classified by examination of hematoxylin-eosin (H&E)-stained slides on biopsy and had subsequent resection specimens were selected. Subtyping of the tumor was based on the resection specimen using the World Health Organization criteria. ΔNp63 was expressed in all 16 SCCs (100%), and was negative in all ACs and LCCs. CK5/6 was positive in 13 of 16 SCCs (81%), and was negative in all ACs and LCCs. TTF-1 was positive in 20 of 25 ACs (80%) and 3 of 7 LCCs (43%), but none of 16 SCCs. Napsin A was positive in 16 of 25 ACs (64%) and was negative in all SCCs and LCCs. Our study shows that a panel including ΔNp63, CK5/6, TTF-1, and napsin A allows correct subclassification of 39 of 48 cases of NSCLC on biopsy and may contribute to refine lung cancer classification in biopsy specimens, remarkably reducing the NSCLC-NOS (not otherwise specified) diagnostic category.