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Higher Levels of the Anti-inflammatory Protein CC10 Are Associated with Improvement in Bronchial Dysplasia and Sputum Cytometric Assessment in Individuals at High Risk for Lung Cancer

Authors' Affiliations: ¹ Cancer Prevention Fellowship Program, Office of Preventive Oncology and ² Lung and Upper Aerodigestive Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, NIH, Bethesda, Maryland; ³ Lung Tumor Group, British Columbia Cancer Agency and the University of British Columbia, Vancouver, British Columbia, Canada; and ⁴ CC10 Sweden AB, Rockville, Maryland

Requests for reprints: Eva Szabo, Lung and Upper Aerodigestive Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, 6130 Executive Boulevard, Room 2132, Bethesda, MD 20892. Phone: 301-435-2456; Fax: 301-480-3924; E-mail: szaboe{at}mail.nih.gov.

Purpose: CC10, a 10-kDa anti-inflammatory protein secreted by bronchiolar Clara cells, is infrequently expressed in non–small cell lung cancer and its overexpression in non–small cell lung cancer cell lines results in a less malignant phenotype. Several lines of evidence have shown that bronchial dysplasia and sputum atypia are predictors of lung cancer. We investigated whether changes in CC10 expression correlate with regression of bronchial dysplasia and/or improvement in sputum abnormalities as measured by image cytometry.

Experimental Design: High-risk smokers enrolled in a chemoprevention trial underwent serial bronchoscopies with biopsies and bronchoalveolar lavage (BAL) collection, sputum assessment by image cytometry, and blood collection. CC10 was measured by competitive ELISA in BAL and plasma. Logistic regression analyses were done to determine the associations between CC10 levels and the improvement in bronchial dysplasia and sputum cytometric assessment.

Results: The net change in the BAL CC10 levels in subjects with improved bronchial lesions or improved sputum cytometry assessment was significantly higher than in those without improvement (P < 0.05). The odds ratio (95% confidence interval) associated with 1-unit increase in CC10 was 2.72 (1.31-5.64) for regression of dysplastic lesions and 2.94 (1.22-7.05) for improvement in sputum cytometry assessment after multivariate adjustment. Plasma CC10 was not significantly associated with either outcome.

Conclusions: Higher BAL CC10 levels are significantly correlated with regression of bronchial dysplasia and improvement in sputum cytometry assessment in smokers with high lung cancer risk. Whether CC10 levels can predict clinical outcomes among high-risk populations warrants further investigation.