Breast Cancer Research and Treatment

, Volume 133, Issue 1, pp 49–59

Co-expression of SNAIL and TWIST determines prognosis in estrogen receptor–positive early breast cancer patients

  • Johanna G. H. van Nes
  • Esther M. de Kruijf
  • Hein Putter
  • Dana Faratian
  • Alison Munro
  • Fiona Campbell
  • Vincent T. H. B. M. Smit
  • Gerrit-Jan Liefers
  • Peter J. K. Kuppen
  • Cornelis J. H. van de Velde
  • John M. S. Bartlett
Preclinical Study

DOI: 10.1007/s10549-011-1684-y

Cite this article as:
van Nes, J.G.H., de Kruijf, E.M., Putter, H. et al. Breast Cancer Res Treat (2012) 133: 49. doi:10.1007/s10549-011-1684-y

Abstract

Epithelial mesenchymal transition (EMT) plays an important role in the development of metastases. One of the hallmarks of EMT is loss of E-cadherin and gain of N-cadherin expression, which are regulated by transcription factors, such as SNAIL, SLUG, and TWIST. We examined the prognostic value of these factors as well as E-cadherin and N-cadherin, in a well-described large cohort of breast cancer patients treated with primary surgery. Analyses were stratified by estrogen receptor (ER) status, because of its crucial role in the regulation of these transcription factors. SNAIL, SLUG, and TWIST expression were examined on a TMA containing 575 breast tumors using immunohistochemistry. Nuclear expression was quantified using a weighted histoscore and classified as high versus low expression, based on the median histoscore. High expression of SNAIL, SLUG, and TWIST was seen in 54, 50, and 50% of tumors, respectively. The level of SNAIL (P = 0.014) and TWIST (P = 0.006) expression was associated with a worse patient relapse-free period, specifically in patients with ER-positive tumors (interaction Cox proportional hazards P = 0.039). Combining both factors resulted in an independent prognostic factor with high discriminative power (both low versus either high: HR 1.15; both low versus both high HR 1.84; P = 0.010). Co-expression of SNAIL–TWIST was associated with low-E-cadherin and high-N-cadherin expression, especially in ER-positive tumors (P = 0.009), suggesting that, through interactions with ER, SNAIL and TWIST may regulate E- and N-cadherin expression, thereby inducing EMT. Our results are indicative that SNAIL and TWIST play a crucial role in EMT through regulation of E- and N-cadherin expression, exclusively in ER-positive breast cancer patients.

Keywords

Early breast cancerPrognostic factorsSNAILSLUGTWIST

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Johanna G. H. van Nes
    • 1
    • 2
  • Esther M. de Kruijf
    • 1
  • Hein Putter
    • 3
  • Dana Faratian
    • 4
  • Alison Munro
    • 4
  • Fiona Campbell
    • 4
  • Vincent T. H. B. M. Smit
    • 5
  • Gerrit-Jan Liefers
    • 1
  • Peter J. K. Kuppen
    • 1
  • Cornelis J. H. van de Velde
    • 1
  • John M. S. Bartlett
    • 4
  1. 1.Department of SurgeryLeiden University Medical CentreLeidenThe Netherlands
  2. 2.Department of Radiation OncologyUniversity Medical Centre Groningen, University of GroningenGroningenThe Netherlands
  3. 3.Department of Medical StatisticsLeiden University Medical CentreLeidenThe Netherlands
  4. 4.Department of Pathology, Endocrine Cancer Group, Edinburgh Cancer Research CentreWestern General HospitalEdinburghUK
  5. 5.Department of PathologyLeiden University Medical CentreLeidenThe Netherlands