title: Prognostic significance of Ape1/ref-1 subcellular localization in non-small cell lung carcinomas.
abstract: OBJECTIVE
  To evaluate the prognostic value of the DNA repair/redox-protein Ape1/ref-1 in a retrospective series of consecutive non-small cell lung carcinomas (NSCLC).
  
  
  METHODS
  Sections from 91 radically resected NSCLC were analyzed for immunohistochemical expression of Ape1/ref-1. For each case 1,000 tumor cells were evaluated to detect nuclear and cytoplasmic reactivity scored as a percentage of positive cells. With respect to sub-cellular localization and percentage of immunoreactive cells, each tumor was classified as "cytoplasmic" or "non cytoplasmic". The survival rate according to Ape1/ref-1 sub-cellular localization was calculated.
  
  
  RESULTS
  The main pattern of Ape1/ref-1 expression was nuclear. No significant difference was observed in Ape1/ref-1 pattern according to histotype (squamous vs adenocarcinoma). Among adenocarcinomas, a cytoplasmic expression of Ape1/ref-1 was significantly associated with poor survival rate in univariate (p=0.01) and multivariate (p=0.07) analyses. In addition, a cytoplasmic expression of the DNA repair protein was also predictive of worse prognosis (log-rank test, p=0.02) in cases with lymph node involvement, regardless of histotype.
  
  
  CONCLUSIONS
  The results suggest a potential role of Ape1/ref-1 sub-cellular localization as a prognostic indicator in patients with NSCLC. In particular, cytoplasmic localization of the protein seems to confer a poor outcome in subgroups of patients with nodal involvement or adenocarcinoma histotype.
authors.affiliation: University of Udine, Italy. fabio.puglisi@med.uniud.it
authors.forename: F
authors.initials: F
authors.lastname: Puglisi
authors.forename: G
authors.initials: G
authors.lastname: Aprile
authors.forename: A M
authors.initials: AM
authors.lastname: Minisini
authors.forename: F
authors.initials: F
authors.lastname: Barbone
authors.forename: P
authors.initials: P
authors.lastname: Cataldi
authors.forename: G
authors.initials: G
authors.lastname: Tell
authors.forename: M R
authors.initials: MR
authors.lastname: Kelley
authors.forename: G
authors.initials: G
authors.lastname: Damante
authors.forename: C A
authors.initials: CA
authors.lastname: Beltrami
authors.forename: C
authors.initials: C
authors.lastname: Di Loreto
mesh_terms: D000368:Aged; D019757:Carbon-Oxygen Lyases / Q000096:biosynthesis / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000473:pathology; D002467:Cell Nucleus / Q000201:enzymology; D003593:Cytoplasm / Q000201:enzymology; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004706:Endodeoxyribonucleases / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D013347:Subcellular Fractions / Q000201:enzymology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D016159:Tumor Suppressor Protein p53; D004706:Endodeoxyribonucleases; D019757:Carbon-Oxygen Lyases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase