title: Different growth patterns of non-small cell lung cancer represent distinct biologic subtypes.
abstract: BACKGROUND
  We have recently shown the prognostic value of growth pattern classification in non-small cell lung cancer. The aim of this study is to validate the hypothesis that these growth patterns have a distinct angiogenic and proliferative profile.
  
  
  METHODS
  Hematoxylin-eosin stained tissue sections of 239 patients with non-small cell lung cancer were classified into growth patterns. One representative tissue section per patient was double immunostained with CD34 and Ki-67 antibodies. Endothelial cell proliferation fraction, tumor cell proliferation fraction, microvessel density, and Chalkley count were assessed at the invading front and the center of the selected tumor section.
  
  
  RESULTS
  According to the growth pattern classification, 161 patients (67.4%) had a destructive, 33 (13.8%) a papillary, and 45 (18.8%) an alveolar growth pattern. There were significant differences in endothelial cell proliferation fraction (p < 0.001), tumor cell proliferation fraction (p < 0.001), microvessel density (p < 0.001), and Chalkley count (p < 0.001) between the growth patterns. Multiple Cox regression analysis showed that a low endothelial cell proliferation fraction was consistently an independent prognostic factor for overall poor (hazard ratio = 0.93; confidence interval: 0.88 to 0.97, p = 0.002) and disease-free survival (hazard ratio = 0.94; confidence interval: 0.89 to 0.98, p = 0.007).
  
  
  CONCLUSIONS
  Growth patterns have a distinct angiogenic and proliferative profile. In non-small cell lung cancer, a low degree of angiogenesis (a low endothelial cell proliferation fraction) is associated with poor prognosis.
authors.affiliation: Department of Thoracic and Vascular Surgery, University Hospital Antwerp, Antwerp, Belgium. peymansardarinia@yahoo.com
authors.forename: Peyman
authors.initials: P
authors.lastname: Sardari Nia
authors.forename: Cecile
authors.initials: C
authors.lastname: Colpaert
authors.forename: Peter
authors.initials: P
authors.lastname: Vermeulen
authors.forename: Joost
authors.initials: J
authors.lastname: Weyler
authors.forename: Francesco
authors.initials: F
authors.lastname: Pezzella
authors.forename: Paul
authors.initials: P
authors.lastname: Van Schil
authors.forename: Eric
authors.initials: E
authors.lastname: Van Marck
mesh_terms: D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D048708:Cell Growth Processes / Q000502:physiology; D049109:Cell Proliferation; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology* / Q000503:physiopathology; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D016019:Survival Analysis