Immunohistochemical Identification of Exocrine and Neuroendocrine Subsets of Large Cell Lung Carcinomas

Formalin fixed, paraffin embedded sections of 52 cases of pulmonary large cell undifferentiated carcinoma (LCUC) as defined in the current WHO classification were studied immunohistochemically to assess features of exocrine and neuroendocrine (NE) differentiation. Monoclonal antibody 44-3A6 was applied to detect a membrane association protein related to exocrine differentiation. A panel of ten neuroendocrine markers including antibodies to synaptophysin, chromogranin A, serotonin, and seven neuropeptides was used to assess NE differentiation. The broad spectrum anticytokeratin antibody PKK1 was used to confirm the epithelial differentiation of these tumors. Exocrine differentiation was detected in 40/52 (77%) of surgically resected LCUC, despite the absence of recognizable glands by light microscopy. Eighteen of 52 (35%) LCUC exhibited NE differentiation; synaptophysin was the most frequently detected NE marker. Cytokeratin immunostaining with PKK1 was demonstrated in 41/52 (79%) cases. Subsets of LCUC were defined based on their expression of exocrine or NE phenotypic markers. Accordingly, 28/52 (54%) LCUC displayed an exocrine phenotype, 6/52 (12%) a NE phenotype, 12/52 (23%) had combined exocrine and NE phenotypes, and 6/52 (12%) exhibited neither phenotype. In this surgical series, there were no significant differences in stage at presentation for the four subsets. Interestingly, two year survival appeared decreased in patients with tumors displaying the "pure" NE phenotype.