283P - MAD2L1 overexpression leads to early metastasis in breast cancer

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Breast Cancer, Early Stage
Translational Research
Presenter Petros Tsantoulis
Citation Annals of Oncology (2014) 25 (suppl_4): iv85-iv109. 10.1093/annonc/mdu327
Authors P. Tsantoulis1, D. Migliorini2, S. Martin-Lluesma1, A. Durigova1, A. Bodmer3, P. Dietrich4, I. Labidi-Galy2
  • 1Oncology, Geneva University Hospitals, 1211 - Geneva/CH
  • 2Medical Oncology, Hopitaux universitaires de Geneve, 1205 - geneva/CH
  • 3Medical Oncology Service, Hôpitaux universitaires de Genève, CH-1211 - Geneva/CH
  • 4Medical Oncology, HUG, CH-1211 - Geneva/CH

Abstract

Aim

Mitotic arrest deficient 2 (MAD2) is an essential spindle assembly checkpoint (SAC) protein. It prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. Its overexpression leads to short survival and chromosomal instability in lung cancer but its significance in breast cancer has not been investigated yet.

Methods

We obtained 7 previously published Affymetrix microarray datasets of breast cancer patients. Probes 203362_s and 1554768_a were mapped on MAD2L1 (MAD2 gene) transcripts and chosen for further analysis. We constructed multivariate Cox proportional hazard survival models of gene expression with distant metastasis-free survival (DMFS). The resulting hazard ratios from each dataset were combined in a meta-analysis (random effects model).

Results

In total, 2,538 patients were included. High expression of MAD2L1 was associated with shorter DMFS (HR = 1.17, 95% CI 1.03-3.67, p = 0.011) after multivariate adjustment for tumor node, size and grade.

Conclusions

This is the first report showing that overexpression of MAD2L1 leads to early metastasis in breast cancer. Since MAD2 is a major gatekeeper of the mitotic mechanism, understanding MAD2L1 pathophysiology could guide the development of new targeted therapies in breast cancer.

Disclosure

All authors have declared no conflicts of interest.