Tissue-Preserving Antibody Cocktails to Differentiate Primary Squamous Cell Carcinoma, Adenocarcinoma, and Small Cell Carcinoma of Lung

Abstract

Context.—With the availability of cell type–specific therapies, differentiating primary lung squamous cell carcinomas (SCCs) and adenocarcinomas (ACAs) has become important. The limitations of small sample size and the need to conserve tissue for additional molecular studies necessitate the use of sensitive and specific marker panels on a single slide.Objective.—To distinguish SCC from ACA and small cell carcinoma (SmCC) of lung using 2 novel tissue-conserving cocktails.Design.—We compared two antibody cocktails, desmoglein 3 + cytokeratin 5/napsin A and p40/thyroid transcription factor 1 (Biocare Medical, Concord, California) in diagnosing SCC and ACA of the lung on tissue microarray, cytology, and surgical specimens. Both lung and nonlung tissue were evaluated on an 1150-core tissue microarray that contained 200 lung cancers. A microarray of 35 SmCCs and 5 small cell SCCs was also evaluated.Results.—A cocktail of desmoglein 3 + cytokeratin 5/napsin A provided diagnostic accuracy in lung cancers with a sensitivity and specificity of 100% in SCCs and a sensitivity of 86% and a specificity of 100% in ACAs. A p40/thyroid transcription factor 1 cocktail showed p40 to have a specificity of 92% and a sensitivity of 93% in SCCs, whereas thyroid transcription factor 1 had a specificity of 100% and a sensitivity of 77% in ACAs. Cell blocks of fine-needle aspiration cytology compared with corresponding surgical (n = 20) specimens displayed similar findings. The p40 was useful in differentiating bladder from prostate carcinoma with 88% sensitivity. Isolated carcinomas from nonlung tissues were desmoglein 3 + cytokeratin 5 positive. Napsin A was positive in 22% of renal tumors as previously observed. Both cocktails were excellent in differentiating SmCCs and small cell SCCs because none of the SmCCs stained with p40.Conclusions.—Both antibody cocktails are excellent in differentiating primary lung ACA from SCC, as well as excluding SmCC and ACAs from all other sites on small specimens. A cocktail of desmoglein 3 + cytokeratin 5/napsin A is slightly superior compared with p40/thyroid transcription factor 1 cocktail.