Evidence of neoangiogenesis and an increase in the number of proliferating cells within the bronchial epithelium of smokers

Cancer. 2002 Oct 1;95(7):1539-45. doi: 10.1002/cncr.10850.


Background: Normal bronchial epithelium gradually acquires cellular and genetic changes that result in the formation of invasive tumors. The objective of this study was to evaluate the degree of proliferative change and the amount of neovascularization in both normal and preneoplastic lesions in smokers who were at high risk for developing lung carcinoma.

Methods: The authors studied bronchial biopsy specimens from 7 nonsmokers and 52 smokers. Immunohistochemical staining of the specimens with antibodies for the presence of p53 protein, Ki-67 and CD34 antigens, and vascular endothelial growth factor was performed. The proliferation index (PI) was assessed by immunohistochemical staining for Ki-67 antigen.

Results: Overexpression of p53 protein was observed frequently in regions of squamous dysplasia and in squamous cell carcinoma tissue. The PI of normal epithelium from smokers was increased compared with nonsmokers, and the difference was statistically significant (P < 0.05). The microvessel count (MC) in normal mucosa obtained from smokers was higher compared with the MC in normal mucosa obtained from nonsmokers (P < 0.05). A significant difference in MC also was observed between regions of squamous metaplasia or dysplasia with projections of capillary loops into the bronchial mucosa and similar lesions without capillary loops (P < 0.005); however, there was no difference in either the PI or the incidence of p53 overexpression between these groups.

Conclusions: These results show that smoking appears to induce both a proliferative response and neovascularization in bronchial mucosa. The projection of capillary loops into the bronchial mucosa also may be a result of neovascularization occurring within the lamina propria of the bronchial wall.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD34 / analysis
  • Carcinoma, Squamous Cell / physiopathology*
  • Cell Division*
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Lung / cytology
  • Lung / pathology*
  • Lung Neoplasms / physiopathology*
  • Male
  • Metaplasia
  • Neovascularization, Pathologic*
  • Precancerous Conditions / pathology*
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / pathology*
  • Smoking / adverse effects*
  • Tumor Suppressor Protein p53 / analysis


  • Antigens, CD34
  • Ki-67 Antigen
  • Tumor Suppressor Protein p53