Stromal cells in phyllodes tumors of the breast are enriched for EZH2 and stem cell marker expression

Yanhong Zhang, Adam L. Liss, Eugene Chung, Lori J. Pierce, Celina G. Kleer

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Phyllodes tumors (PTs) of the breast are fibroepithelial neoplasms with stromal hypercellularity, which is the basis for their classification as benign, borderline, and malignant. The histologic diagnosis of PTs is often difficult, and the pathological features may not always predict clinical behavior. The pathobiology of PT remains poorly understood. Enhancer of Zeste 2 (EZH2) epigenetically regulates cell-type identity, cellular differentiation, and breast cancer stem cells. EZH2 exerts oncogenic functions in breast cancer and is associated with metastasis. We hypothesized that in PTs, EZH2 and the stem cell marker ALDH1 may be expressed in stromal cells and may be associated with their degree of differentiation. Forty PTs were histologically characterized at our institution following the World Health Organization criteria. We investigated the expression of EZH2 and ALDH1 by immunohistochemistry and recorded as percentage of positive epithelial and stromal cells. EZH2 was positive when over 10 % of cells exhibited nuclear staining; ALDH1 was positive when over 5 % of cells had cytoplasmic staining. Of the 40 PTs, 24 (60 %) were histologically benign, 8 (20 %) borderline, and 8 (20 %) malignant. Stromal EZH2 was significantly associated with the diagnosis of malignant PT, as it was detected in 1 of 24 (4 %) benign, 3 of 8 (37.5 %) borderline, and 5 of 8 (62.5 %) malignant tumors. Stromal EZH2 was significantly associated with stromal overgrowth (p = 0.01), atypia (p = 0.01), hypercellularity (p = 0.01), and mitoses (p = 0.02), all features of malignant PT. Stromal EZH2 and ALDH1 were significantly associated with grade of PT (p = 0.01 and p < 0.05 respectively). In conclusion, EZH2 and ALDH1 expression in the stroma of PT may mark malignant progression and may be helpful to distinguish histologically benign from borderline and malignant tumors in challenging cases. Our study also suggests that PTs contain mesenchymal stem cells, shedding light into the pathogenesis of these tumors.

Original languageEnglish (US)
Pages (from-to)21-28
Number of pages8
JournalBreast Cancer Research and Treatment
Volume158
Issue number1
DOIs
StatePublished - Jul 1 2016

Fingerprint

Phyllodes Tumor
Stromal Cells
Breast
Stem Cells
Neoplastic Stem Cells
Breast Neoplasms
Fibroepithelial Neoplasms
Staining and Labeling
Neoplasms
Mesenchymal Stromal Cells
Mitosis

Keywords

  • ALDH1
  • Breast cancer
  • EZH2
  • Phyllodes tumors
  • Stem cell
  • Stromal cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Stromal cells in phyllodes tumors of the breast are enriched for EZH2 and stem cell marker expression. / Zhang, Yanhong; Liss, Adam L.; Chung, Eugene; Pierce, Lori J.; Kleer, Celina G.

In: Breast Cancer Research and Treatment, Vol. 158, No. 1, 01.07.2016, p. 21-28.

Research output: Contribution to journalArticle

Zhang, Yanhong ; Liss, Adam L. ; Chung, Eugene ; Pierce, Lori J. ; Kleer, Celina G. / Stromal cells in phyllodes tumors of the breast are enriched for EZH2 and stem cell marker expression. In: Breast Cancer Research and Treatment. 2016 ; Vol. 158, No. 1. pp. 21-28.
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abstract = "Phyllodes tumors (PTs) of the breast are fibroepithelial neoplasms with stromal hypercellularity, which is the basis for their classification as benign, borderline, and malignant. The histologic diagnosis of PTs is often difficult, and the pathological features may not always predict clinical behavior. The pathobiology of PT remains poorly understood. Enhancer of Zeste 2 (EZH2) epigenetically regulates cell-type identity, cellular differentiation, and breast cancer stem cells. EZH2 exerts oncogenic functions in breast cancer and is associated with metastasis. We hypothesized that in PTs, EZH2 and the stem cell marker ALDH1 may be expressed in stromal cells and may be associated with their degree of differentiation. Forty PTs were histologically characterized at our institution following the World Health Organization criteria. We investigated the expression of EZH2 and ALDH1 by immunohistochemistry and recorded as percentage of positive epithelial and stromal cells. EZH2 was positive when over 10 {\%} of cells exhibited nuclear staining; ALDH1 was positive when over 5 {\%} of cells had cytoplasmic staining. Of the 40 PTs, 24 (60 {\%}) were histologically benign, 8 (20 {\%}) borderline, and 8 (20 {\%}) malignant. Stromal EZH2 was significantly associated with the diagnosis of malignant PT, as it was detected in 1 of 24 (4 {\%}) benign, 3 of 8 (37.5 {\%}) borderline, and 5 of 8 (62.5 {\%}) malignant tumors. Stromal EZH2 was significantly associated with stromal overgrowth (p = 0.01), atypia (p = 0.01), hypercellularity (p = 0.01), and mitoses (p = 0.02), all features of malignant PT. Stromal EZH2 and ALDH1 were significantly associated with grade of PT (p = 0.01 and p < 0.05 respectively). In conclusion, EZH2 and ALDH1 expression in the stroma of PT may mark malignant progression and may be helpful to distinguish histologically benign from borderline and malignant tumors in challenging cases. Our study also suggests that PTs contain mesenchymal stem cells, shedding light into the pathogenesis of these tumors.",
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