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

• Published in: Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2007-11, Vol.16 (11), p.2425-2431
• Main Authors: MILLER, York E, BLATCHFORD, Patrick, HIRSCH, Fred R, KITTELSON, John, DAE SUNG HYUN, KEITH, Robert L, KENNEDY, Timothy C, WOLF, Holly, BYERS, Tim, BUNN, Paul A, LEWIS, Marina T, FRANKLIN, Wilbur A
• Format: Article
• Language: English
• Subjects: Aged; Biological and medical sciences; Biomarkers; Biopsy; Bronchi - metabolism; Bronchi - pathology; Chemoprevention; Cross-Sectional Studies; Epithelial Cells - metabolism; Epithelial Cells - pathology; Female; Humans; Ki-67 Antigen - biosynthesis; Ki-67 Antigen - genetics; Ki-67 Antigen - metabolism; Lung Cancer; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Pneumology; Proliferation; Pulmonary Disease, Chronic Obstructive - blood; Pulmonary Disease, Chronic Obstructive - metabolism; Pulmonary Disease, Chronic Obstructive - pathology; Sex Factors; Smoking - metabolism; Smoking - pathology; Tumors; Tumors of the respiratory system and mediastinum
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-07-0220

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)