ESPL1 is a candidate oncogene of luminal B breast cancers

Breast Cancer Res Treat. 2014 Aug;147(1):51-9. doi: 10.1007/s10549-014-3070-z. Epub 2014 Aug 3.


ESPL1/separase is a putative oncogene of luminal B breast cancers. Histoclinical correlations of its expression have never been explored in large series of breast tumors, and specifically in the luminal subtype. In a pooled series of invasive breast carcinomas profiled using DNA microarrays, we identified 3,074 luminal cases, including 1,307 luminal B tumors, in which we searched for correlations between ESPL1 mRNA expression and molecular and histoclinical features. Compared to normal breast samples, ESPL1 was overexpressed in 52 % of luminal tumors, and much more frequently in luminal B (83 %) than luminal A tumors (29 %). In luminal breast cancers, higher ESPL1 expression was associated with poor-prognosis criteria (age ≤ 50 years, ductal type, advanced stage, large tumor size, lymph node-positive status, high grade, PR-negative status, luminal B subtype) and with poor metastasis-free survival in both uni- and multivariate analyses. This independent prognostic value was also observed in luminal B tumors only, and persisted when compared with gene expression signatures (PAM50, Recurrence Score, Mammaprint, EndoPredict) currently proposed to refine the indications of adjuvant chemotherapy in hormone receptor-positive/HER2-negative breast cancer. We also confirmed the observations made with experimental mouse models: ESPL1-overexpressing luminal tumors showed complex genomic profiles and molecular features of chromosomal instability and loss of tumor suppressor genes (P53 and Rb). Our results reinforce the idea that ESPL1 is a candidate oncogene in luminal B cancers. Its expression may help improve the prognostication. Inhibiting ESPL1 may represent a promising therapeutic approach for these poor-prognosis tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / genetics*
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Lobular / genetics*
  • Carcinoma, Lobular / mortality
  • Carcinoma, Lobular / pathology
  • Female
  • Follow-Up Studies
  • Gene Dosage
  • Humans
  • Mice
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Receptor, ErbB-2 / genetics
  • Receptors, Estrogen / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Separase / genetics*
  • Survival Rate


  • Biomarkers, Tumor
  • RNA, Messenger
  • Receptors, Estrogen
  • Receptor, ErbB-2
  • ESPL1 protein, human
  • Separase