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Epithelial–mesenchymal transition and cancer stem cell interactions in breast phyllodes tumours: immunohistochemical evaluation of EZH2, EZR, HMGA2, CD24 and CD44 in correlation with outcome analysis
  1. Syed Salahuddin Ahmed1,
  2. Jeffrey Chun Tatt Lim1,
  3. Aye Aye Thike1,
  4. Jabed Iqbal1,
  5. Puay Hoon Tan2
  1. 1Anatomical Pathology, Singapore General Hospital, Division of Pathology, Singapore
  2. 2Pathology, Singapore General Hospital, Division of Pathology, Singapore
  1. Correspondence to Dr Syed Salahuddin Ahmed, Anatomical Pathology, Singapore General Hospital Division of Pathology, Singapore 169856, Singapore; syed.salahuddin.ahmed{at}singhealth.com.sg

Abstract

Aim Phyllodes tumours (PTs) categorised as benign, borderline and malignant, account for 1% of all breast tumours. Histological assessment does not always predict tumour behaviour, hindering determination of the clinical course and management.

Epithelial–mesenchymal transition (EMT) is an important process during embryogenesis. Dysregulation of EMT causes loss of cell polarity, decreased intercellular adhesion, increased motility and invasiveness, promoting tumour progression. Similarly, cancer stem cells (CSCs) promote tumour growth, resistance and recurrence. The aim of this study is to evaluate expression of CSC markers; enhancer of zeste homolog 2 (EZH2), CD24 and CD44 and EMT associated proteins; ezrin (EZR) and high-mobility group AT-hook 2 (HMGA2) in PTs.

Method Uing tissue microarray sections, immunohistochemistry was performed on 360 PTs. Epithelial and stromal expressions of EZH2, EZR, HMGA2, CD24 and CD44 were evaluated to assess their impact on disease progression and behaviour in correlation with clinicopathological parameters.

Results Stromal expression of EZH2, EZR and HMGA2 was observed in 73 (20.3%), 53 (14.7%) and 28 (7.8%) of tumours, epithelial expression in 121 (35.9%), 3 (0.8%) and 351 (97.5%) tumours, respectively. CD24 and CD44 staining was absent in both components.

Conclusion Expression of biomarkers correlated significantly with aggressive tumour traits such as stromal hypercellularity, atypia, mitoses and permeative tumour borders.

Stromal expression of EZH2 and EZR shortened disease-free survival and overall survival; HMGA2 expression did not alter patient survival. EZH2 and EZR may thus be useful in predicting PT behaviour.

  • breast neoplasms
  • immunohistochemistry
  • breast

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Footnotes

  • Handling editor Cheok Soon Lee.

  • Contributors SSA: conception or design of the work, analysis of the biomarkers, analysis or interpretation of data, drafting the work for important intellectual content. JCTL: immunohistochemical staining, analysis or interpretation of data, revising it critically for important intellectual content. AAT: substantial contributions to the analysis or interpretation of data, revising it critically for important intellectual content. JI: immunohistochemical analysis, drafting the work or revising it critically for important intellectual content. PHT: substantial contributions to the conception or design of the work, or the acquisition, analysis or interpretation of data. Drafting the work or revising it critically for important intellectual content.

  • Funding This study was supported by Singapore General Hospital (SGH) Research Grant (SRG#10/2013).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Institutional Review Board approval (CIRF Ref: 2013/457/B)

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article. This study is not a clinical trial. All data were obtained from the files of department of pathology.

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