TTF-1, cytokeratin 7, 34 beta E12, and CD56/NCAM immunostaining in the subclassification of large cell carcinomas of the lung

We selected a 4-stain immunopanel including thyroid transcription factor (TTF)-1, cytokeratin (CK) 7, 34betaE12, and CD56/neural cell adhesion molecule (NCAM) to subclassify a series of 45 pulmonary large cell carcinomas (LCCs) on bronchial biopsy. All cases consisted of a large tumor cell proliferation with abundant cytoplasm, vesicular nuclei, and prominent nucleoli. Immunohistochemically, 27 tumors (60%) were subclassified as adenocarcinoma (TTF-1+/CK7+, 24; CK7+ only, 3), 10 (22%) as squamous cell carcinoma (34betaE12+ only), and 4(9%) as LCC with neuroendocrine differentiation (CD56+, variably stained with TTF-1 and CK7, 34betaE12-). In 4 cases, the tumors coexpressed CK7 and 34betaE12 (3 cases) or were completely unstained (1 case). Surgically resected tumors matched exactly with the corresponding original biopsy specimens in 21 of 23 cases; consistent CD56 expression was a reliable marker in confirming a diagnosis of large cell neuroendocrine carcinoma even on biopsy. Our results suggest that the proposed 4-stain set of commercially available markers might help subclassify LCC even in small biopsy material, validating expression-profiling studies aimed at lung cancer classification and permitting more consistent patient enrollment for trials with targeted treatments.