Evaluation of Napsin A, Cytokeratin 5/6, p63, and Thyroid Transcription Factor 1 in Adenocarcinoma Versus Squamous Cell Carcinoma of the Lung

Context.-The distinction of lung adenocarcinoma from other types of primary lung malignancies is important clinically. Accurate morphologic classification is often hindered because 70% of lung cancers are diagnosed on limited fine-needle aspiration or transbronchial biopsy specimens. Although thyroid transcription factor 1 (TTF-1) has historically been the most specific marker for lung adenocarcinoma, a relatively new marker, napsin A, has recently been shown to be more sensitive and specific than TTF-1. Objective.-To find the most cost-effective panel to reliably distinguish lung adenocarcinoma from squamous cell carcinoma. Design.-A total of 291 lung cancers were evaluated morphologically (197 adenocarcinomas [75%]; 66 squamous cell carcinomas [25%]; 28 cases could not be classified into either and were dropped). Immunohistochemistry for napsin A, Cytokeratin 5/6, p63, and TTF-1 was performed on a formalin-fixed tissue microarray obtained from Toyama, Japan. Cases were scored as positive or negative against a negative control. Results.-Napsin A had 83% sensitivity and 98% specificity and TTF-1 had 60% sensitivity and 98% specificity for adenocarcinoma. Cytokeratin 5/6 had 53% sensitivity and 96% specificity and p63 had 95% sensitivity and 86% specificity for squamous cell carcinoma. A panel of napsin A and p63 has a specificity of 94% and a sensitivity of 96% for distinguishing adenocarcinoma from squamous cell carcinoma. Conclusions.-The source of the antibody is important in avoiding false-negative results. The most cost-effective tissue-preserving panel for small biopsy specimens in the differential diagnosis of lung adenocarcinoma versus squamous cell carcinoma is a combination of p63 and napsin A. (Arch Pathol Lab Med. 2012;136:155-162; doi: 10.5858/arpa.2011-0232-OA)