title: Immunohistochemical detection of neuroendocrine differentiation in non-small-cell lung cancer and its clinical implications.
abstract: OBJECTIVE
  The purpose of this study was to prospectively assess the clinical implications of neuroendocrine (NE) differentiation in non-small-cell lung cancer (NSCLC) tumors.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine and Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, 160 Kou Minami-Umemoto-cho, Matsuyama, Ehime 791-0288, Japan. ysegawa@shikoku-cc.go.jp
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Segawa
authors.forename: Saburo
authors.initials: S
authors.lastname: Takata
authors.forename: Masanori
authors.initials: M
authors.lastname: Fujii
authors.forename: Isao
authors.initials: I
authors.lastname: Oze
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kato
authors.forename: Atsuko
authors.initials: A
authors.lastname: Ogino
authors.forename: Eisaku
authors.initials: E
authors.lastname: Komori
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sawada
authors.forename: Motohiro
authors.initials: M
authors.lastname: Yamashita
authors.forename: Rieko
authors.initials: R
authors.lastname: Nishimura
authors.forename: Norihiro
authors.initials: N
authors.lastname: Teramoto
authors.forename: Shigemitsu
authors.initials: S
authors.lastname: Takashima
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018278:Carcinoma, Neuroendocrine / Q000473:pathology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology*; D002454:Cell Differentiation; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D055099:Neuroendocrine Cells / Q000737:chemistry / Q000473:pathology*; D011446:Prospective Studies