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

¹ Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, Denver Veterans Affairs Medical Center, Departments of ² Preventive Medicine and Biometrics, ³ Medicine, HealthOne, and ⁴ Division of Medical Oncology, Department of Medicine, and ⁵ Department of Pathology, University of Colorado at Denver and Health Sciences Center, University of Colorado Comprehensive Cancer Center, Denver, Colorado; and ⁶ Catholic University of Daegu, Daegu, South Korea

Requests for reprints: York E. Miller, Department of Medicine, University of Colorado, Pulmonary 111A, Denver Veterans Affairs Medical Center, 1055 Clermont Street, Denver, CO 80220. Phone: 303-393-2869; Fax: 303-393-4639. E-mail: york.miller{at}uchsc.edu

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

Experimental Design: 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 expresssion 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. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2425–31)