Bronchial Epithelial Ki-67 Index Is Related to Histology, Smoking, and Gender, but Not Lung Cancer or Chronic Obstructive Pulmonary Disease

Abstract

To determine whether increased bronchial epithelial proliferation is associated with histology, smoking status, gender, age, chronic obstructive pulmonary disease (COPD), or lung cancer. 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 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%). 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.