Interaction between p53 mutation and a somatic HDMX biomarker better defines metastatic potential in breast cancer

Research output: Contribution to journalArticlepeer-review

Authors

  • Anna M Grawenda
  • Elen K Møller
  • Suzanne Lam
  • Emmanouela Repapi
  • Amina F A S Teunisse
  • Grethe I G Alnæs
  • Anne-Lise Børresen-Dale
  • Vessela N Kristensen
  • Colin R Goding
  • Aart G Jochemsen
  • Hege Edvardsen

Colleges, School and Institutes

Abstract

TP53 gene mutation is associated with poor prognosis in breast cancer, but additional biomarkers that can further refine the impact of the p53 pathway are needed to achieve clinical utility. In this study, we evaluated a role for the HDMX-S/FL ratio as one such biomarker, based on its association with other suppressor mutations that confer worse prognosis in sarcomas, another type of cancer that is surveilled by p53. We found that HDMX-S/FL ratio interacted with p53 mutational status to significantly improve prognostic capability in patients with breast cancer. This biomarker pair offered prognostic utility that was comparable with a microarray-based prognostic assay. Unexpectedly, the utility tracked independently of DNA-damaging treatments and instead with different tumor metastasis potential. Finally, we obtained evidence that this biomarker pair might identify patients who could benefit from anti-HDM2 strategies to impede metastatic progression. Taken together, our work offers a p53 pathway marker, which both refines our understanding of the impact of p53 activity on prognosis and harbors potential utility as a clinical tool.

Details

Original languageEnglish
Pages (from-to)698-708
Number of pages11
JournalCancer Research
Volume75
Issue number4
Early online date3 Feb 2015
Publication statusPublished - 15 Feb 2015

Keywords

  • Biomarkers, Tumor/biosynthesis, Breast Neoplasms/drug therapy, Cell Cycle Proteins, Disease-Free Survival, Female, Gene Expression Regulation, Neoplastic, Humans, Lymphatic Metastasis/genetics, Mutation, Neoplasm Staging, Nuclear Proteins/biosynthesis, Proto-Oncogene Proteins/biosynthesis, Tumor Suppressor Protein p53/biosynthesis