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The Prognostic Significance of Neuroendocrine Markers and Carcinoembryonic Antigen in Patients with Resected Stage I and II Non-Small Cell Lung Cancer¹

Departments of Medicine [S. L. G., N. B. N., G. P. G., S. B., S. O.], Surgery [L. J. K., L. J. V., M. J. C.], and Pathology [A. H. T., A. O.], Veterans Administration Medical Center, State University of New York-Health Science Center, Syracuse, New York 13210

Non-small cell lung cancer with neuroendocrine differentiation may represent a subset of patients with a more aggressive (like small cell lung cancer) or less aggressive (like carcinoid) biological behavior. To investigate their prognostic significance, immunohistochemical stains for 4 neuroendocrine markers (neuron-specific enolase, chromogranin A, Leu-7, and synaptophysin) and carcinoembryonic antigen (CEA) were studied in 260 patients with surgically resected stage I and II non-small cell lung cancer. The following percentages of cases were positive for each marker: neuron-specific enolase, 70.0%; chromogranin A, 14.2%; Leu-7, 7.7%; synaptophysin, 11.2%; and CEA, 68.5%. Sixty-one (23.5%) were positive for 2 neuroendocrine markers. When compared to adenocarcinoma, squamous cell carcinoma displayed lower positivity for CEA and 2 neuroendocrine markers. There was no significant difference in stage, site of relapse (distant versus local), disease-free, or overall survival for each marker individually or for those with 2 neuroendocrine markers. Multivariate analysis showed that higher nodal stage (N₁ versus N_o), tumor stage (T₂ versus T₁), older age, and the presence of mucin predicted for poorer overall survival. Neuroendocrine markers and CEA were not of prognostic significance in this group of patients with resected stage I and II non-small cell lung cancer.

¹ Supported by the Veterans Administration Research Service.

² To whom requests for reprints should be addressed, at Veterans Administration Medical Center, 800 Irving Avenue, Syracuse, NY 13210.

Received 11/19/93. Accepted 3/28/94.

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