title: Prognostic significance of neuroendocrine differentiation in adenocarcinoma of the lung.
abstract: BACKGROUND
  The relative incidence of adenocarcinoma of the lung is increasing and some patients with lung carcinoma, detected at an early stage, still develop recurrent disease despite complete resection of the tumor. Recently, neuroendocrine differentiation in large cell carcinoma of the lung has been reported to be of prognostic significance. Therefore, we have evaluated the prognostic significance of neuroendocrine differentiation in adenocarcinoma of the lung.
  
  
  METHODS
  A total of 90 resected specimens of adenocarcinoma of the lung measuring 3 cm or less (T1 N0 M0 or T2 N0 M0) were reviewed histologically and immunohistochemical staining was performed to determine the degree of neuroendocrine differentiation.
  
  
  RESULTS
  Seven adenocarcinomas exhibited neuroendocrine differentiation in 10% or more of tumor cells. The disease-free survival rate for these patients was significantly lower than that of patients with tumors exhibiting neuroendocrine differentiation in less than 10% of tumor cells or with absent neuroendocrine differentiation (p < 0.0005). Other conventional pathologic factors such as vascular invasion (p < 0.0005), lymphatic invasion (p < 0.05), and pleural involvement (p < 0.05) were also of prognostic significance. In multivariate analysis, the presence of 10% or more neuroendocrine marker-positive tumor cells, vascular invasion, and lymphatic invasion were found to be significantly adverse prognostic factors (p = 0.0162, p = 0.0111, and p = 0.0173, respectively).
  
  
  CONCLUSIONS
  Neuroendocrine differentiation of tumor cells is a prognostic factor in lung adenocarcinoma. It is suggested that the identification of neuroendocrine differentiation as well as vascular invasion by tumor in small peripheral adenocarcinoma of the lung may predict the prognosis of these patients.
authors.affiliation: Department of Basic Pathology, Graduate School of Medicine, Chiba University, Japan. kenzo@med.m.chiba-u.ac.jp
authors.forename: Kenzo
authors.initials: K
authors.lastname: Hiroshima
authors.forename: Akira
authors.initials: A
authors.lastname: Iyoda
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Shibuya
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Toyozaki
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Haga
authors.forename: Takehiko
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ohwada
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology*; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009489:Neurosecretion; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor