Increase of EZH2 Expression in Bronchiolar Epithelial Cells in Smoking-Related Diseases of the Lung.
Jennifer J Findeis-Hosey, Loralee A McMahon, Qi Yang, Faqian Li, Haodong Xu. University of Rochester, NY
Background: Epigenetic modifications of histones play essential roles in tumorogenesis. Enhancer of zeste homolog 2 (EZH2), a key component of polycomb repressive complex 2, mediates histone H3 methylation at lysine 27. EZH2 has been demonstrated via immunohistochemical staining to be expressed in multiple human malignancies, including squamous cell carcinoma of the lung. However, its role in early tumorogenesis remains unclear. Previously we demonstrated scattered sparse EZH2 expression in basal bronchiolar cells. The aim of this study was to determine if there is differential EZH2 expression in the bronchiolar epithelial cells of patients with a smoking history and smoking-related lung diseases, specifically respiratory bronchiolitis (RB) and desquamative interstitial pneumonia (DIP) as compared to those of patients with no history of smoking.
Design: Twenty-five surgically resected lung specimens were immunohistochemically studied using a monoclonal antibody against EZH2 (Leica), including 9 cases of RB, 7 cases of DIP, and 9 cases from non-smokers. Clinical history was examined to confirm that all patients with RB and DIP were current or past smokers. For each case two bronchioles with similar luminal circumferences were examined. For each bronchiole, 100 contiguous non-neoplastic, non-metaplastic bronchiolar epithelial cells were examined and the percentage of EZH2 positive cells was recorded. The percentage of EZH2 positive cells was averaged for each case. Nuclear staining was considered positive for EZH2. A p value of <0.05, as determined by Fisher's exact test, was considered statistically significant.
Results: Immunohistochemical studies showed that the majority of the EZH2 positive cells were localized in the basal layer of bronchiolar epithelium. The values (Mean±SD) of EZH2 positive bronchiolar epithelial cells were 5.11±1.16% in non-smoking patients, 21.71±7.27% in patients with DIP, and 16.72±3.50% in patients with RB. There was no significant difference between the percentage of EZH2 positive bronchiolar epithelial cells in the RB and DIP groups (p=0.51). However, there was a statistically significant difference in EZH2 positivity in bronchiolar epithelial cells in patients with RB and DIP as compared to examined cases from non-smokers without these pathologies (p=0.01).
Conclusions: Our study shows that smoking-related respiratory diseases (RB and DIP) are associated with an increase of EZH2 expression in the bronchiolar epithelial cells, which indicates smoking induced EZH2 expression may be involved in the early stage of carcinogenesis.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 262, Wednesday Morning