Activating Enhancer-Binding Protein-2β Nucleolar Localization Predicts Poor Survival After Stage I Non-Small Cell Lung Cancer Resection

Abstract

Activating enhancer-binding protein-2β (AP2β) is a transcription factor involved in apoptosis. The purpose of the current study was to assess the cellular location and level of AP2β in non-small cell lung cancer (NSCLC) and normal lung tissue and investigate whether the level and localization of AP2β expression is predictive of overall survival in patients with stage I NSCLC. We performed immunohistochemical analysis of tissue microarrays (TMAs) prepared from stage I NSCLC specimens with adjacent normal lung tissue from two independent sets of patients who underwent lung resection with curative intent at our institution. The AP2β intensity was assessed in TMAs, and AP2β staining patterns were classified as either diffuse or nucleolar in the TMAs. The AP2β intensity and localization were analyzed for correlation with patients' survival. Immunohistochemical analysis of TMAs showed that the intensity of AP2β immunohistochemical staining did not correlate with overall survival. When location of AP2β was analyzed in TMAs, all of the normal lung tissue had diffuse pattern of AP2β. In the first set of NSCLC, patients with nucleolar pattern had a significantly lower 5-year survival rate than patients with diffuse pattern (67% versus 100%; p=0.004); this finding was confirmed in the second set (64% versus 91%; p=0.02). Multivariate analysis revealed that nucleolar pattern was an independent predictor of poor overall survival in both sets. The AP2β, which is located in the nucleoplasm in normal lung tissue, is found in either nucleoplasm or nucleoli in NSCLC. The patients with AP2β in the nucleoli had poor survival compared with patients with AP2β in the cytoplasm.