THE PROGNOSTIC-SIGNIFICANCE OF NEUROENDOCRINE MARKERS AND CARCINOEMBRYONIC ANTIGEN IN PATIENTS WITH RESECTED STAGE-I AND STAGE-II NONSMALL CELL LUNG-CANCER

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 greater than or equal to 2 neuroendocrine markers. When compared to adenocarcinoma, squamous cell carcinoma displayed lower positivity for CEA and greater than or equal to 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 greater than or equal to 2 neuroendocrine markers. Multivariate analysis showed that higher nodal stage (N-1 versus N-0), tumor stage (T-2 versus T-1), 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.