title: Activating enhancer-binding protein-2β nucleolar localization predicts poor survival after stage I non-small cell lung cancer resection.
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.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. mpkim@tmhs.org
authors.forename: Min P
authors.initials: MP
authors.lastname: Kim
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: B Nebiyou
authors.initials: BN
authors.lastname: Bekele
authors.forename: Adriana
authors.initials: A
authors.lastname: Lopez
authors.forename: Abha
authors.initials: A
authors.lastname: Khanna
authors.forename: Jie Qing
authors.initials: JQ
authors.lastname: Chen
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Spitz
authors.forename: Carmen
authors.initials: C
authors.lastname: Behrens
authors.forename: Luisa
authors.initials: L
authors.lastname: Solis
authors.forename: Marnie
authors.initials: M
authors.lastname: Wismach
authors.forename: Lin
authors.initials: L
authors.lastname: Ji
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.forename: Jack A
authors.initials: JA
authors.lastname: Roth
authors.forename: Ruth L
authors.initials: RL
authors.lastname: Katz
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002467:Cell Nucleus / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D013781:Texas / Q000453:epidemiology; D050656:Transcription Factor AP-2 / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C493677:TFAP2B protein, human; D050656:Transcription Factor AP-2