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Tumor Biology

, Volume 33, Issue 3, pp 787–798 | Cite as

Molecules involved in epithelial–mesenchymal transition and epithelial–stromal interaction in phyllodes tumors: implications for histologic grade and prognosis

  • Ji Eun Kwon
  • Woo-Hee Jung
  • Ja Seung Koo
Research Article

Abstract

The aim of this study was to investigate the expression of molecules associated with epithelial–mesenchymal transition (EMT) and epithelial–stromal interactions (ESI) and to evaluate their roles in phyllodes tumors (PTs). Tissue microarrays (TMAs) were constructed from 207 PT specimens (157 benign, 34 borderline and 16 malignant). The presence of EMT-related markers including N-cadherin, Twist, TGF-beta, HMGA2, S100A4 and Ezrin as well as ESI-related molecules such as SDF1 and CXCR4 among the TMAs was assessed immunohistochemically. Immunohistochemical results were analyzed in terms of clinicopathologic parameters. For higher grade PTs, expressions of Twist (p < 0.001), HMGA2 (p = 0.005), S100A4 (p < 0.001), CXCR4 (p < 0.001) and TGF-beta (p < 0.001) were higher. As PTs showed higher stromal cellularity, higher stromal mitosis, stromal overgrowth and infiltrative tumor margin, the expressions of Twist, HMGA2 and CXCR4 in the stromal component thereof were increased (p < 0.05). High Twist expression in the stromal component was associated with shorter disease-free survival (DFS) and overall survival (OS) (p < 0.001) as well as shorter OS in multivariate COX analysis (p = 0.031, odds ratio: 24.6). In conclusion, the expressions of Twist, HMGA2, TGF-beta and S100A4, which are EMT-associated molecules, and CXCR4, an ESI-associated molecule, were increased in the stromal component of advanced grade PTs. Further, high expression of Twist in the stromal component was correlated with poorer prognoses.

Keywords

Breast Phyllodes tumor Grade Twist 

Notes

Acknowledgements

This work was supported by a Yonsei University Research Fund of 2011.

Conflicts of interest

None.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2011

Authors and Affiliations

  1. 1.Department of PathologyInje University Sanggye Paik HospitalSeoulSouth Korea
  2. 2.Brain Korea 21 Project for Medical SciencesYonsei University College of MedicineSeoulSouth Korea
  3. 3.Department of PathologyYonsei University College of Medicine, Severance HospitalSeoulSouth Korea

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