title: Pulmonary large cell neuroendocrine carcinoma demonstrates high proliferative activity.
abstract: BACKGROUND
  In 1999, the World Health Organization classified large cell neuroendocrine carcinoma as a variant of large cell carcinoma and this has been categorized as lying between atypical carcinoid and small cell lung carcinoma in terms of clinical aggressiveness.
  
  
  METHODS
  We analyzed the proliferative activity of stage 1 large cell neuroendocrine carcinoma derived from patients with primary lung cancer who underwent surgical resection and compared the results with stage 1 classic large cell carcinoma cases. The mitotic rate was counted in ten high-power fields of light microscope. Immunohistochemical staining using anti-Ki-67 antibody was performed. The Ki-67 labeling index, expressed as a percentage of positive cells, was determined by light microscopy with random counting of at least 1000 tumor nuclei. The expression of P53 and Bcl-2 was examined and compared.
  
  
  RESULTS
  The mitotic rate of large cell neuroendocrine carcinoma cases was significantly higher than that of classic large cell carcinoma cases. The Ki-67 labeling index of stage 1 large cell neuroendocrine carcinoma cases was significantly higher than that of stage 1 classic large cell carcinoma cases. Immunohistochemical expression of P53 in large cell neuroendocrine carcinoma and classic large cell carcinoma was comparable. However, large cell neuroendocrine carcinoma exhibited a significantly higher expression of Bcl-2 than classic large cell carcinoma. The disease specific disease-free survival for patients with stage 1 large cell neuroendocrine carcinoma was significantly lower than that for patients with stage 1 classic large cell carcinoma.
  
  
  CONCLUSIONS
  Large cell neuroendocrine carcinoma appears to be more clinically aggressive than classic large cell carcinoma with these findings indicating that large cell neuroendocrine carcinoma has a higher level of proliferative activity than classic large cell carcinoma.
authors.affiliation: Department of Thoracic Surgery, Chiba, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Iyoda
authors.forename: Kenzo
authors.initials: K
authors.lastname: Hiroshima
authors.forename: Yasumitsu
authors.initials: Y
authors.lastname: Moriya
authors.forename: Teruaki
authors.initials: T
authors.lastname: Mizobuchi
authors.forename: Mizuto
authors.initials: M
authors.lastname: Otsuji
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sekine
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Shibuya
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iizasa
authors.forename: Yukio
authors.initials: Y
authors.lastname: Saitoh
authors.forename: Takehiko
authors.initials: T
authors.lastname: Fujisawa
mesh_terms: D000328:Adult; D000368:Aged; D018287:Carcinoma, Large Cell / Q000737:chemistry / Q000473:pathology* / Q000601:surgery; D018278:Carcinoma, Neuroendocrine / Q000737:chemistry / Q000473:pathology* / Q000601:surgery; D002455:Cell Division; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008175:Lung Neoplasms / Q000737:chemistry / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53