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Comparative Study
. 2011 Sep;92(3):1044-50.
doi: 10.1016/j.athoracsur.2011.04.029.

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

Min P Kim  1 , 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
Affiliations
Comparative Study

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

Min P Kim et al. Ann Thorac Surg. 2011 Sep.

Abstract

Background: 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.

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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Figures

FIGURE 1
FIGURE 1
Both A549 (a) and H1299 (b) lung cancer cell have more AP2β staining compared to control immortalized HBEC (c) cells. Western-blot analysis showed that AP2β protein expression is upregulated in the A549 and H1299 lung cancer cells compared to control immortalized HBEC cells (d).
FIGURE 2
FIGURE 2
Diffuse nuclear AP2β staining characterized by nucleoplasm staining without nucleoli staining in NSCLC (a) Nucleolar AP2β staining characterized by the staining of several small nucleoli or a single large macronucleoli with or without nucleoplasm staining in NSCLC (b). All tumor-adjacent normal lung tissue specimens had diffuse nuclear AP2β staining (c).
FIGURE 3
FIGURE 3
In the initial set, patients who had NSCLC with a nucleolar AP2β pattern had a significantly lower 5-year survival rate than patients who had NSCLC with a diffuse AP2β pattern (67% vs. 100%; p = 0.009).
FIGURE 4
FIGURE 4
In the validation set, patients who had NSCLC with a nucleolar AP2β pattern had a significantly lower 5-year survival rate than patients who had NSCLC with a diffuse AP2β pattern (64% vs. 91%; p = 0.0211).
See this image and copyright information in PMC

Comment in

  • Invited commentary.
    D'Amico TA. D'Amico TA. Ann Thorac Surg. 2011 Sep;92(3):1050. doi: 10.1016/j.athoracsur.2011.04.075. Ann Thorac Surg. 2011. PMID: 21871298 No abstract available.

References

    1. Nesbitt JC, Putnam JB, Jr., Walsh GL, et al. Survival in early-stage non-small cell lung cancer. Ann Thorac Surg. 1995;60(2):466–72. - PubMed
    1. Yan P, Benhattar J, Seelentag W, et al. Immunohistochemical localization of hTERT protein in human tissues. Histochem Cell Biol. 2004;121(5):391–7. - PubMed
    1. Etheridge KT, Banik SS, Armbruster BN, et al. The nucleolar localization domain of the catalytic subunit of human telomerase. J Biol Chem. 2002;277(27):24764–70. - PubMed
    1. Wang L, Soria JC, Kemp BL, et al. hTERT expression is a prognostic factor of survival in patients with stage I non-small cell lung cancer. Clin Cancer Res. 2002;8(9):2883–9. - PubMed
    1. Eckert D, Buhl S, Weber S, et al. The AP-2 family of transcription factors. Genome Biol. 2005;6(13):246. - PMC - PubMed

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