Immunohistochemical neuroendocrine differentiation is an independent prognostic factor in surgically resected large cell carcinoma of the lung.

The clinical significance of neuroendocrine (NE) differentiation is unclear in large cell carcinoma (LCC) of the lung. Fifty-five surgically resected carcinomas of the lung with an original pathologic diagnosis of LCC were reviewed histologically with special attention to NE morphology. Antibodies against neural cell adhesion molecule (NCAM), chromogranin A (CGA) and synaptophysin (SY) were used to confirm the NE differentiation. Thirteen (24%) cases were classified as large cell neuroendocrine carcinoma, 9 (16%) as LCC with NE differentiation, and 33 (60%) as pure LCC. There was no significant difference in overall survival between the three groups. When the 55 carcinomas were divided into three groups depending on the number of NE marker expression, there was significantly better overall survival in the NE > or = 2 (P = 0.02). Multivariate analysis proved NE > or = 2 was an independent predictor of survival. The number of NE markers was more important in terms of survival than histological sub-classification. Copyright 2002 Elsevier Science Ireland Ltd.