Neuroendocrine differentiation is an independent prognostic factor in chemotherapy-treated nonsmall cell lung carcinoma

Cancer. 1996 Apr 1;77(7):1284-91. doi: 10.1002/(SICI)1097-0142(19960401)77:7<1284::AID-CNCR9>3.0.CO;2-I.


Background: Neuroendocrine differentiation can be identified in 10-30% of patients with nonsmall cell lung carcinoma (NSCLC) by immunohistochemical or electron microscopic techniques. However, its clinical significance is not well established.

Methods: Tumors from 107 patients with Stage IIIA, IIIB, and IV NSCLC treated with cisplatin/etoposide with or without hydrazine in the North Central Cancer Treatment Group and Mayo Clinic protocols were analyzed immunohistochemically with antibodies to chromogranin A (CGA), Leu 7 (CD 57), and synaptophysin (SY). These results were compared with clinical outcomes.

Results: Keratin AE1/AE3, used as a control, was positive in 99.1% of cases; 34.6% had positive staining for at least 1 neuroendocrine marker, and 11.3% had positive staining for 2 or more markers. CGA was positive in 4.7%, Leu 7 in 18.7%, and SY in 24.3% of cases. A significant increase in survival was seen in patients with tumors expressing any one neuroendocrine marker or any combination of neuroendocrine markers (P < or = 0.01). There was no correlation between the presence of neuroendocrine differentiation and either response to chemotherapy or time to disease progression (P > 0.3), nor was there any correlation between chemotherapy response, time to progression, or survival with staining intensity or percent of cells positive per case.

Conclusions: Neuroendocrine differentiation may be of prognostic significance in patients with advanced stage NSCLC treated with chemotherapy.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Differentiation
  • Cisplatin / administration & dosage
  • Disease Progression
  • Etoposide / administration & dosage
  • Female
  • Humans
  • Hydrazines / administration & dosage
  • Immunohistochemistry
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neuroendocrine Tumors / drug therapy*
  • Neuroendocrine Tumors / pathology*
  • Prognosis
  • Staining and Labeling / methods


  • Hydrazines
  • hydrazine
  • Etoposide
  • Cisplatin