title: Evidence of neoangiogenesis and an increase in the number of proliferating cells within the bronchial epithelium of smokers.
abstract: 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.
authors.affiliation: Department of Basic Pathology, Graduate School of Medicine, Chiba University, Chiba, 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: Hidehisa
authors.initials: H
authors.lastname: Hoshino
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Haga
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Toyozaki
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Shiba
authors.forename: Masayuki
authors.initials: M
authors.lastname: Baba
authors.forename: Takehiko
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ohwada
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000503:physiopathology*; D002455:Cell Division; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008168:Lung / Q000166:cytology / Q000473:pathology*; D008175:Lung Neoplasms / Q000503:physiopathology*; D008297:Male; D008679:Metaplasia; D009389:Neovascularization, Pathologic; D011230:Precancerous Conditions / Q000473:pathology*; D020545:Respiratory Mucosa / Q000166:cytology / Q000473:pathology*; D012907:Smoking / Q000009:adverse effects*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D018952:Antigens, CD34; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53