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Breast Cancer Research and Treatment

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11.06.2016 | Preclinical study

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

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

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2016

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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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Titel: Stromal cells in phyllodes tumors of the breast are enriched for EZH2 and stem cell marker expression
verfasst von: Yanhong Zhang
Adam L. Liss
Eugene Chung
Lori J. Pierce
Celina G. Kleer
Publikationsdatum: 11.06.2016
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 1/2016
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-016-3853-5

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

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