Prognostic significance of Ape1/ref-1 subcellular localization in non-small cell lung carcinomas.
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.
Puglisi
F
F
University of Udine, Italy. fabio.puglisi@med.uniud.it
Aprile
G
G
Minisini
A M
AM
Barbone
F
F
Cataldi
P
P
Tell
G
G
Kelley
M R
MR
Damante
G
G
Beltrami
C A
CA
Di Loreto
C
C
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
D016159:Tumor Suppressor Protein p53; D004706:Endodeoxyribonucleases; D019757:Carbon-Oxygen Lyases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase