Activating enhancer-binding protein-2β nucleolar localization predicts poor survival after stage I non-small cell lung cancer resection

激活增强子结合蛋白-2β 核仁定位预测 I 期非小细胞肺癌切除术后生存率较低

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作者:Min P Kim, Ying Chen, B Nebiyou Bekele, Adriana Lopez, Abha Khanna, Jie Qing Chen, Margaret R Spitz, Carmen Behrens, Luisa Solis, Marnie Wismach, Lin Ji, Ignacio I Wistuba, Jack A Roth, Ruth L Katz

Background

Activating enhancer-binding protein-2β (AP2β) is a transcription factor involved in apoptosis. The

Conclusions

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.

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 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.

Results

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. Conclusions: 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.

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