Prognostic significance of Ape1/ref-1 subcellular localization in non-small cell lung carcinomas

Fabio Puglisi, Giuseppe Aprile, Alessandro M. Minisini, Fabio Barbone, Palmina Cataldi, Gianluca Tell, Mark R. Kelley, Giuseppe Damante, Carlo A. Beltrami, Carla Di Loreto

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72 Scopus citations

Abstract

Purpose: 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). Patients and 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)4041-4049
Number of pages9
JournalAnticancer Research
Volume21
Issue number6 A
StatePublished - Dec 1 2001
Externally publishedYes

Keywords

  • Ape1/ref-1
  • DNA repair
  • Immunohistochemistry
  • Multivariate analysis
  • Non-small cell lung cancer
  • Prognosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Puglisi, F., Aprile, G., Minisini, A. M., Barbone, F., Cataldi, P., Tell, G., Kelley, M. R., Damante, G., Beltrami, C. A., & Di Loreto, C. (2001). Prognostic significance of Ape1/ref-1 subcellular localization in non-small cell lung carcinomas. Anticancer Research, 21(6 A), 4041-4049.