• York E Miller, Patrick Blatchford, Dae Sung Hyun, Robert L Keith, Timothy C Kennedy, Holly Wolf, Tim Byers, Paul A Bunn, Marina T Lewis, Wilbur A Franklin, Fred R Hirsch, and John Kittelson.
• 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
• Cancer Epidemiol. Biomarkers Prev. 2007 Nov 1; 16 (11): 2425-31.

PurposeTo determine whether increased bronchial epithelial proliferation is associated with histology, smoking status, gender, age, chronic obstructive pulmonary disease (COPD), or lung cancer.Experimental DesignCross-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.ResultsResults 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%).ConclusionsSmoking 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.

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