Abstract 231: Gene expression analysis of persistent and regressive bronchial dysplasia identifies polo-like kinase 1 (PLK1) and epoxide hydrolase 3 (EPHX3) as potential mediators of malignant progression

Introduction: Gene expression microarray analysis was employed to identify alterations that distinguish persistent from regressive bronchial dysplasia (BD). BD is a precursor of squamous cell carcinoma (SCC), and persistent BDs represent a high risk subset of these lesions. A potential role for promotion of genomic instability in persistence of BD is suggested by the overexpression of polo-like kinase 1 (PLK1), which abrogates G2-M checkpoint DNA damage repair, and epoxide hydrolase 3 (EPHX3), which converts tobacco smoke derived pro-carcinogens to mutagens. Methods and Results: Sixty-three frozen baseline biopsies were classified, based on the presence or absence of BD in follow-up biopsies, into persistent BD, regressive BD, progressive non-dysplasia and stable non-dysplasia groups. ANOVA statistical analysis with a false discovery rate of 10% revealed 318 differentially expressed genes between persistent and regressive BD, whereas all other intergroup comparisons except persistent BD versus stable non-dysplasia revealed no or very few (