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Immunohistochemical detection of neuroendocrine differentiation in non-small-cell lung cancer and its clinical implications



The purpose of this study was to prospectively assess the clinical implications of neuroendocrine (NE) differentiation in non-small-cell lung cancer (NSCLC) tumors.


This study accrued subjects suspected to have lung cancer who underwent diagnostic bronchoscopy. Bronchoscopically-biopsied specimens were subjected to routine pathologic examination, and immunohistochemical studies were then performed if lung cancer was diagnosed. Chromogranin-A, synaptophysin, neural cell adhesion molecule, and Leu7 were used to demonstrate NE differentiation.


A total of 280 subjects were accrued to this study over a period of 2 years. Among them, 149 subjects were assessable for this study, and 130 were diagnosed as having NSCLC tumors (55 adenocarcinomas, 50 squamous cell carcinomas, 24 NSCLCs not otherwise specified, and 1 typical carcinoid). Large cell NE carcinoma was not observed in this study. Immunohistochemically, NE differentiation was detected in 16% of NSCLC tumors excluding typical carcinoid. By status of NE differentiation of NSCLC tumors, progression-free survivals were similar in 73 patients undergoing non-surgical treatment (positive, n = 10; negative, n = 63) and 43 patients undergoing surgical resection (positive, n = 8; negative, n = 35), respectively. Overall survival of patients with NE-positive tumors appeared to be favorable both for those undergoing non-surgical treatment and those undergoing surgical resection, though the differences in survival were not significant (P = 0.11 and 0.35, respectively).


NE differentiation was detected in 16% of NSCLC tumors in our study. However, the prognostic implications of the presence of this feature could not be clearly determined in this study.

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This study was supported in part by a grant from the Ministry of Health, Labor, and Welfare of Japan (No. 15–15).

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Correspondence to Yoshihiko Segawa.

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Segawa, Y., Takata, S., Fujii, M. et al. Immunohistochemical detection of neuroendocrine differentiation in non-small-cell lung cancer and its clinical implications. J Cancer Res Clin Oncol 135, 1055 (2009).

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  • Non-small-cell lung carcinoma
  • Neuroendocrine lung tumor
  • Neuroendocrine differentiation
  • Immunohistochemistry