title: Bronchial epithelial Ki-67 index is related to histology, smoking, and gender, but not lung cancer or chronic obstructive pulmonary disease.
abstract: OBJECTIVE
  To determine whether increased bronchial epithelial proliferation is associated with histology, smoking status, gender, age, chronic obstructive pulmonary disease (COPD), or lung cancer.
  
  
  METHODS
  Cross-sectional study of 113 subjects undergoing white light and autofluorescence bronchoscopy: 27 never smokers; 27 current or ex-smokers with normal spirometry; 31 current or ex-smokers with COPD; and 28 current, ex-, or never smokers with lung cancer. Ki-67 expression was determined by immunohistochemistry on all evaluable biopsy sites without carcinoma. Relationships between Ki-67 index (percentage of epithelial cells expressing Ki-67), demographic variables, smoking, histology, and the presence of COPD and/or lung cancer were determined.
  
  
  RESULTS
  Results for both maximal and mean Ki-67 index are similar, so only the former are reported. Average maximal Ki-67 index was higher in current smokers than either ex-smokers or never smokers (48.0% versus 30.6% versus 22.6%; P<0.001). Males had higher Ki-67 index than females (39.9% versus 23.6%; P<0.001). Compared with subjects without disease (Ki-67 index=30.0%), maximal Ki-67 index was not significantly elevated (P=0.44) in subjects with either lung cancer (Ki-67=39.1%) or COPD (Ki-67=38.9%).
  
  
  CONCLUSIONS
  Smoking status, bronchial histology, and gender were significantly associated with Ki-67 index. No increase in Ki-67 index was found in the nonmalignant epithelium of patients with lung cancer or COPD. Although Ki-67 index may provide insight into the short-term effects of chemoprevention agents on cell proliferation, its lack of association with lung cancer or COPD raises question regarding its utility as a lung cancer risk biomarker.
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, Denver Veterans Affairs Medical Center, University of Colorado at Denver, Denver, Colorado 80220, USA. york.miller@uchsc.edu
authors.forename: York E
authors.initials: YE
authors.lastname: Miller
authors.forename: Patrick
authors.initials: P
authors.lastname: Blatchford
authors.forename: Dae Sung
authors.initials: DS
authors.lastname: Hyun
authors.forename: Robert L
authors.initials: RL
authors.lastname: Keith
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Kennedy
authors.forename: Holly
authors.initials: H
authors.lastname: Wolf
authors.forename: Tim
authors.initials: T
authors.lastname: Byers
authors.forename: Paul A
authors.initials: PA
authors.lastname: Bunn
authors.forename: Marina T
authors.initials: MT
authors.lastname: Lewis
authors.forename: Wilbur A
authors.initials: WA
authors.lastname: Franklin
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
authors.forename: John
authors.initials: J
authors.lastname: Kittelson
mesh_terms: D000368:Aged; D001706:Biopsy; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D003430:Cross-Sectional Studies; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D012737:Sex Factors; D012907:Smoking / Q000378:metabolism* / Q000473:pathology
chemical_list: D019394:Ki-67 Antigen