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

Background. Activating enhancer-binding protein-2 beta (AP2 beta) is a transcription factor involved in apoptosis. The purpose of the current study was to assess the cellular location and level of AP2 beta in non-small cell lung cancer (NSCLC) and normal lung tissue and investigate whether the level and localization of AP2 beta expression is predictive of overall survival in patients with stage I NSCLC. Methods. 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 AP2 beta intensity was assessed in TMAs, and AP2 beta staining patterns were classified as either diffuse or nucleolar in the TMAs. The AP2 beta intensity and localization were analyzed for correlation with patients' survival. Results. Immunohistochemical analysis of TMAs showed that the intensity of AP2 beta immunohistochemical staining did not correlate with overall survival. When location of AP2 beta was analyzed in TMAs, all of the normal lung tissue had diffuse pattern of AP2 beta. 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. Conclusions. The AP2 beta, which is located in the nucleoplasm in normal lung tissue, is found in either nucleoplasm or nucleoli in NSCLC. The patients with AP2 beta in the nucleoli had poor survival compared with patients with AP2 beta in the cytoplasm. (Ann Thorac Surg 2011;92:1044-50) (C) 2011 by The Society of Thoracic Surgeons