PLoS ONE (Jan 2013)

Prognostic significance of ESR1 gene amplification, mRNA/protein expression and functional profiles in high-risk early breast cancer: a translational study of the Hellenic Cooperative Oncology Group (HeCOG).

  • George Pentheroudakis,
  • Vassiliki Kotoula,
  • Anastasia G Eleftheraki,
  • Eleftheria Tsolaki,
  • Ralph M Wirtz,
  • Konstantine T Kalogeras,
  • Anna Batistatou,
  • Mattheos Bobos,
  • Meletios A Dimopoulos,
  • Eleni Timotheadou,
  • Helen Gogas,
  • Christos Christodoulou,
  • Kyriaki Papadopoulou,
  • Ioannis Efstratiou,
  • Chrisoula D Scopa,
  • Irene Papaspyrou,
  • Dimitrios Vlachodimitropoulos,
  • Helena Linardou,
  • Epaminontas Samantas,
  • Dimitrios Pectasides,
  • Nicholas Pavlidis,
  • George Fountzilas

DOI
https://doi.org/10.1371/journal.pone.0070634
Journal volume & issue
Vol. 8, no. 7
p. e70634

Abstract

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BackgroundDiscrepant data have been published on the incidence and prognostic significance of ESR1 gene amplification in early breast cancer.Patients and methodsFormalin-fixed paraffin-embedded tumor blocks were collected from women with early breast cancer participating in two HeCOG adjuvant trials. Messenger RNA was studied by quantitative PCR, ER protein expression was centrally assessed using immunohistochemistry (IHC) and ESR1 gene copy number by dual fluorescent in situ hybridization probes.ResultsIn a total of 1010 women with resected node-positive early breast adenocarcinoma, the tumoral ESR1/CEP6 gene ratio was suggestive of deletion in 159 (15.7%), gene gain in 551 (54.6%) and amplification in 42 cases (4.2%), with only 30 tumors (3%) harboring five or more ESR1 copies. Gene copy number ratio showed a significant, though weak correlation to mRNA and protein expression (Spearman's Rho ConclusionsESR1 gene deletion and amplification do not constitute per se prognostic markers, instead they can be classified to distinct prognostic groups according to their protein-mediated functional status.