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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.

Authors
  • Ahmed, Syed Salahuddin1
  • Lim, Jeffrey Chun Tatt2
  • Thike, Aye Aye2
  • Iqbal, Jabed2
  • Tan, Puay Hoon3
  • 1 Anatomical Pathology, Singapore General Hospital, Division of Pathology, Singapore [email protected] , (Singapore)
  • 2 Anatomical Pathology, Singapore General Hospital, Division of Pathology, Singapore. , (Singapore)
  • 3 Pathology, Singapore General Hospital, Division of Pathology, Singapore. , (Singapore)
Type
Published Article
Journal
Journal of Clinical Pathology
Publisher
BMJ
Publication Date
May 01, 2022
Volume
75
Issue
5
Pages
316–323
Identifiers
DOI: 10.1136/jclinpath-2020-207068
PMID: 33627375
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. 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. 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. 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. © Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.

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