Expression and prognostic significance of APE1/Ref-1 and NPM1 proteins in high-grade ovarian serous cancer

Am J Clin Pathol. 2014 Mar;141(3):404-14. doi: 10.1309/AJCPIDKDLSGE26CX.

Abstract

Objectives: To correlate the expression profile of human apurinic endonuclease/redox factor 1 (APE1/Ref-1) with that of nucleolar/nucleoplasmic protein nucleophosmin 1 (NPM1) in association with the aggressiveness and progression of high-grade ovarian serous cancer.

Methods: Retrospective study analyzing a tissue microarray of 73 women affected by high-grade ovarian serous cancer. Protein expression was assessed by immunohistochemistry on primary tumor masses and synchronous peritoneal metastases if present.

Results: APE1/Ref-1 and NPM1 showed a significant correlation in ovarian serous cancer. Patients with a poorer outcome showed a significant overexpression of nuclear NPM1 protein. A Cox proportional hazards multivariate regression model revealed NPM1 expression to be independently significant for overall survival in high-grade ovarian serous cancers after correcting for stage, age, cytoreduction completeness, and platinum resistance.

Conclusions: APE1/Ref-1 interacts with NPM1 to control the DNA damage repair system, and it is likely that this interaction plays a defining role in high-grade ovarian serous carcinoma. A high NPM1 immunohistochemical expression was independently correlated with a shorter survival period and thus appears to be an important prognostic factor.

Keywords: APE1/Ref-1; NPM1; Ovarian cancer; Prognostic factors; Survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cystadenocarcinoma, Serous / diagnosis*
  • Cystadenocarcinoma, Serous / metabolism
  • Cystadenocarcinoma, Serous / pathology
  • DNA Repair
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / metabolism*
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Grading
  • Nuclear Proteins / metabolism*
  • Nucleophosmin
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Retrospective Studies

Substances

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