title: Neuroendocrine differentiation is an independent prognostic factor in chemotherapy-treated nonsmall cell lung carcinoma.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: J T
authors.initials: JT
authors.lastname: Schleusener
authors.forename: H D
authors.initials: HD
authors.lastname: Tazelaar
authors.forename: S H
authors.initials: SH
authors.lastname: Jung
authors.forename: S S
authors.initials: SS
authors.lastname: Cha
authors.forename: P J
authors.initials: PJ
authors.lastname: Cera
authors.forename: J L
authors.initials: JL
authors.lastname: Myers
authors.forename: E T
authors.initials: ET
authors.lastname: Creagan
authors.forename: R M
authors.initials: RM
authors.lastname: Goldberg
authors.forename: R F
authors.initials: RF
authors.lastname: Marschke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology*; D002454:Cell Differentiation; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000008:administration & dosage; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000473:pathology*; D011379:Prognosis; D013194:Staining and Labeling / Q000379:methods
chemical_list: D006834:Hydrazines; C029424:hydrazine; D005047:Etoposide; D002945:Cisplatin