Transcription factors WT1 and p53 combined: a prognostic biomarker in ovarian cancer

Br J Cancer. 2018 Aug;119(4):462-470. doi: 10.1038/s41416-018-0191-x. Epub 2018 Jul 30.

Abstract

Background: New approaches to ovarian cancer are needed to improve survival. Wilms' tumour 1 (WT1) is a tumour-associated antigen expressed in many ovarian cancers. P53 is also often altered. The clinical significance of the combined expression of these two transcription factors has not been studied.

Methods: One hundred ninety-six ovarian tumours were classified histopathologically. Tumours were stained for WT1 and p53 immunohistochemically. Stains were analysed according to tumour type, grade and FIGO stage. Kaplan-Meier analyses on 96 invasive carcinomas determined whether categorical variables were related to survival.

Results: WT1 and p53 were related to ovarian tumour type, grade, FIGO stage and patient survival. Uniform nuclear p53 expression was associated with invasion and WT1 expression was associated with advanced grade, FIGO stage and poor survival. When WT1 and p53 were both in the age-adjusted Cox model, WT1 was significant while p53 was not. When we combined tumours expressing WT1 and p53, then adjusted for age and tumour subtype, the hazard ratio compared to tumours without WT1 and with normal p53 was 2.70; when adjusted for age and FIGO stage, the hazard ratio was 2.40.

Conclusions: WT1, an antigen target, is a biomarker for poor prognosis, particularly when combined with altered p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Cell Nucleus / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Prognosis
  • Retrospective Studies
  • Tumor Suppressor Protein p53 / metabolism*
  • Up-Regulation*
  • WT1 Proteins / metabolism*

Substances

  • Biomarkers, Tumor
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • WT1 Proteins
  • WT1 protein, human