Cytology applications of p63 and TTF-1 immunostaining in differential diagnosis of lung cancers

The pathologic distinction of small cell from non‐small cell‐lung carcinoma is of considerable therapeutic significance. In particular, the ability to distinguish poorly differentiated non‐small‐cell lung cancer from small‐cell lung carcinoma (SCLC) is at times difficult based upon morphology alone; available immunohistochemical markers such as neuroendocrine markers are of limited utility. We have demonstrated the role of p63 and thyroid transcription factor‐1 (TTF‐1) in the differential diagnosis of poorly differentiated squamous‐cell carcinoma (PDSCC) versus SCLC, mostly in biopsy samples (Wu et al., American Journal of Clinical Pathology 2003;119:696–702). Here, we examine further the utility of this panel in cytologic cell‐block samples of lung cancers including both primary and metastatic cancers of pulmonary origin, and cases of nonpulmonary cancers metastatic to lung in which differential diagnoses included a lung primary. Four‐micron thick sections of 30 alcohol‐fixed paraffin‐embedded cell blocks from 14 lung FNAs, 6 liver FNAs, 3 bronchial washings, 1 subcarinal lymph node FNA, 1 iliac lymph node FNA, 1 pelvic mass FNA, 1 neck lymph node FNA, 1 adrenal FNA, and 1 pleural effusion were deparaffinized and stained with monoclonal antibodies reactive to p63 (1:800, Santa Cruz Biotechnology) and TTF‐1 (1:50, Dako). Slides were stained for p63 using a streptavidin‐biotin kit (BioGenex) and diaminobenzidine as chromagen, and counterstained with hematoxylin. Slides were stained for TTF‐1 using a Dako Autostainer. Thirty cases were examined, including 8 primary SCLCs, 8 extra‐pulmonary metastases of lung SCLCs, 4 PDSCCs and 4 primary pulmonary adenocarcinomas, and 6 nonpulmonary adenocarcinomas metastatic to lung or other sites. Fifteen out of 16 (94%) SCLC cases were p63−/TTF‐1+, ranging in intensity from focal–weak to diffuse–strong; 1/16 SCLCs from a bronchial washing was p63−/TTF‐1− but synaptophysin was positive. All 4 primary lung adenocarcinoma cases were p63−/TTF‐1+; contrasting with nonpulmonary adenocarcinomas that were all p63−/TTF‐1−. All 4 PDSCC cases were p63+/TTF‐1−. The panel of p63 and TTF‐1 appears to be useful in the diagnostic evaluation of cytologic cell‐block samples of pulmonary malignancy. Diagn. Cytopathol. 2005;33:223–227. © 2005 Wiley‐Liss, Inc.