Molecular classification of breast phyllodes tumors: Validation of the histologic grading scheme and insights into malignant progression

Mei Kim Ang, Aik Seng Ooi, Aye Aye Thike, Patrick Tan, Zhongfa Zhang, Karl Dykema, Kyle Furge, Bin Tean Teh, Puay Hoon Tan

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Phyllodes tumors of the breast are rare fibroepithelial neoplasms with a potential for recurrence. Current histological classification is not always predictive of clinical behavior. The aim of this study was to identify genetic changes associated with the development of borderline and malignant phyllodes tumors in an Asian population, and to assess if genetic data supported the categorization of these tumors into the existing three grades of benign, borderline, and malignant. Expression profiling of 21 phyllodes tumors (6 benign, 10 borderline, 5 malignant) was performed using Affymetrix U133Plus 2.0 GeneChips®. Gene expression among benign, borderline, and malignant tumors was compared and a 29 gene list was able to classify them according to their histologic grade. Among these 29 genes are those responsible for matrix formation, cell adhesion, epidermis formation, and cell proliferation. Comparative genomic microarray analysis showed that the most common chromosomal alteration associated with borderline and malignant tumors was 1q gain, and an increasing number of chromosomal changes was noted with increasing histological grade. Upregulation of HOXB13 was seen in malignant relative to borderline phyllodes tumors and further investigated by immunohistochemistry in a corresponding set of formalin-fixed, paraffin-embedded tumors. HOXB13 protein overexpression was found to be correlated with stromal hypercellularity and atypia (P = 0.03, P = 0.039, respectively) and may be implicated in the development of malignant phyllodes tumors.

Original languageEnglish (US)
Pages (from-to)319-329
Number of pages11
JournalBreast Cancer Research and Treatment
Volume129
Issue number2
DOIs
StatePublished - Sep 1 2011
Externally publishedYes

Keywords

  • Comparative genomic microarray analysis
  • Gene expression
  • Histological grade
  • Malignant progression
  • Phyllodes tumors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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