Different growth patterns of non-small cell lung cancer represent distinct biologic subtypes

Ann Thorac Surg. 2008 Feb;85(2):395-405. doi: 10.1016/j.athoracsur.2007.08.054.


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.

MeSH terms

  • Adult
  • Aged
  • Biopsy, Needle
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Cell Growth Processes / physiology
  • Cell Proliferation*
  • Cohort Studies
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology*
  • Neovascularization, Pathologic / pathology*
  • Neovascularization, Pathologic / physiopathology
  • Probability
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Assessment
  • Sensitivity and Specificity
  • Statistics, Nonparametric
  • Survival Analysis