INTRODUCTION: The clinical course of dysplastic bronchial lesions is variable. While some regress, others progress to invasive carcinoma. We sought to identify how variations in inflammatory infiltrates might influence the clinical outcome of dysplastic bronchial lesions.
METHODS AND RESULTS: Gene expression microarray analyses identified 318 genes that distinguish persistent from regressive bronchial dysplastic lesions. Pathway analysis utilizing this genelist was performed using Ingenuity© software. Gene expression data showed several inflammation related pathways with statistically different levels of activity in persistent versus regressive lesions. Expression of genes associated with CD4 positive T-cells and HLA-DRA positive macrophages were both increased in regressive lesions. To further investigate these findings, a similar set of progressive and regressive lesions were selected for immunohistochemical (IHC) analysis. For each biopsy, IHC for T-cell markers CD3, CD4 and CD8 and macrophage marker CD68 was performed. Immunohistochemically positive inflammatory cell subsets were counted in a single high power field corresponding to the focus of maximum inflammation. For each marker, separate counts for epithelium and stroma-associated inflammation were performed. Preliminary IHC data (n=6) shows a strong trend towards increased numbers of macrophages in the dysplastic epithelium of regressive lesions (4.6 fold increase, p=0.082).
CONCLUSION: Our findings suggest that differences in inflammatory cell subsets may distinguish persistent and regressive bronchial dysplasia. Preliminary data points to CD4 positive T-cells and intraepithelial macrophages as differentiating factors that correlate with regression.
Citation Format: Mary C. O'Keefe, Lori Dwyer-Nield, Michael Edwards, Robert L. Keith, Wilbur A. Franklin, Michio Sugita, York E. Miller, Micah Friedman, Meredith Tennis, Kevin S. Choo, Gregory Hickey, Jeannine Porter, Storey Wilson, Andrea Osypuk, Mary Weiser, Adrie van Bokhoven, Mark Geraci, Raphael Nemenoff, Daniel T. Merrick. Variations in the composition of inflammatory infiltrates are associated with persistence or regression of bronchial dysplasia. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1675. doi:10.1158/1538-7445.AM2014-1675