The expression profile and prognostic value of APE/Ref-1 and NPM1 in high-grade serous ovarian adenocarcinoma

APMIS. 2017 Oct;125(10):857-862. doi: 10.1111/apm.12733. Epub 2017 Aug 2.

Abstract

To analyze the expression trends and clinical significance of Apurinic/Apyrimidinic Endodeoxyribonuclease 1 (APE1/Ref-1) and Nucleophosmin (NPM1) proteins in high-grade serous ovarian adenocarcinoma (HGSC). The expressions of APE1/Ref-1 and NPM1 proteins in 94 patients with HGSC were determined using the immunohistochemical (IHC) method, and their relationships with clinicopathological features were analyzed by the χ2 test or Fisher's exact test. The follow-up data, Cox proportional hazards univariate and multivariate survival analyses were integrated to evaluate the prognostic factors affecting patients with HGSC. In the normal fallopian tubes, APE1/Ref-1 and NPM1 protein were mainly distributed in the nuclear. The HGSC experienced changes in the cellular localization of APE1/Ref-1 and NPM1 protein expressions, which were abnormally expressed in the cytoplasm. The rates of abnormal cytoplasmic expression of APE1/Ref-1 and NPM1 proteins in 94 patients with HGSC were 69.1% and 73.4%, respectively, which were significantly higher than the normal fallopian tube tissues (p < 0.05). The abnormal cytoplasmic APE1/Ref-1 and NPM1 are significantly correlated with the lymph node metastasis, chemosensitivity, FIGO staging, and prognosis. The COX multivariate survival analysis showed that the abnormal expression of APE1/Ref-1 protein, FIGO staging, and lymph node metastasis are independent prognostic factors. Collectively, the abnormal cytoplasmic APE1/Ref-1 and NPM1 proteins are associated with the oncogenic progression and chemoresistance of HGSC, and predict a poor prognosis.

Keywords: APE1/Ref-1; NPM1; high-grade serous ovarian adenocarcinoma; prognosis.

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / pathology*
  • Adult
  • Aged
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / analysis*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / genetics
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Nuclear Proteins / analysis*
  • Nuclear Proteins / genetics
  • Nucleophosmin
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / pathology*
  • Prognosis

Substances

  • NPM1 protein, human
  • Nuclear Proteins
  • Nucleophosmin
  • APEX1 protein, human
  • DNA-(Apurinic or Apyrimidinic Site) Lyase