Malignant phyllodes tumors display mesenchymal stem cell features and aldehyde dehydrogenase/disialoganglioside identify their tumor stem cells

Lin, Jin-Jin; Huang, Chiun‐Sheng; Yu, John; Liao, Guo‐Shiou; Lien, Han‐Chung; Hung, Jung‐Tung; Lin, Ruey‐Jen; Chou, Fen‐Pi; Yeh, Kun‐Tu; Yu, Alice L.

doi:10.1186/bcr3631

Cited by 38 publications

(34 citation statements)

References 39 publications

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“…In addition, these tumors appear to have significant intratumoral heterogeneity . Recent data have shown malignant PTs to display mesenchymal stem cell features with ability to be induced to or spontaneously undergo differentiation to other lineages . This correlates with previous reports of heterologous differentiation in PT, among which lipomatous differentiation appears most frequent .…”

Section: Discussionsupporting

confidence: 86%

Heterologous Liposarcomatous Differentiation in Malignant Phyllodes Tumor is Histologically Similar but Immunohistochemically and Molecularly Distinct from Well-differentiated Liposarcoma of Soft Tissue

2016

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Malignant phyllodes tumor (PT) infrequently displays heterologous differentiation, and when present is most often liposarcomatous. We identified five cases of malignant PT with regions identical to well-differentiated liposarcoma (WDLS) of soft tissue and evaluated them for MDM2 and CDK4 gene expression and amplification using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively. Despite indistinguishable morphology all cases of malignant PT with WDLS-like liposarcomatous differentiation were negative for MDM2 and CDK4 IHC and FISH, supporting different underlying pathogenesis.

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Section: Discussionsupporting

confidence: 86%

Heterologous Liposarcomatous Differentiation in Malignant Phyllodes Tumor is Histologically Similar but Immunohistochemically and Molecularly Distinct from Well-differentiated Liposarcoma of Soft Tissue

2016

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“…Similar to metaplastic carcinomas, malignant PT showed enrichment for cancer stem cell-related biological processes. 50 In another study by Ang et al, 32 a heat map generated from 29 genes showed 3 distinct groups of benign, borderline, and malignant tumors, consistent with histologic classifications. The discrepancy in these studies is largely due to the smaller size of cohort studies with smaller numbers of borderline and malignant PT, and may also reflect differences in the criteria used for classifying PT.…”

Section: Molecular/genetic Featuresmentioning

confidence: 74%

Phyllodes Tumor of the Breast: Histopathologic Features, Differential Diagnosis, and Molecular/Genetic Updates

Zhang

Kleer

2016

Archives of Pathology &Amp; Laboratory Medicine

203

204

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Context.-Phyllodes tumor (PT) of the breast is a rare fibroepithelial neoplasm with risks of local recurrence and uncommon metastases. The classification proposed by the World Health Organization for PTs into benign, borderline, and malignant is based on a combination of several histologic features. The differential diagnosis between PT and fibroadenoma and the histologic grading of PT remain challenging. In addition, the molecular pathogenesis of PT is largely unknown.Objective.-To provide an updated overview of pathologic features, diagnostic terminology, and molecular alterations of PT.Data Sources.-Current English literature related to PT of the breast.Conclusions.-Phyllodes tumor shows a wide spectrum of morphology. There are no clearly distinct boundaries between PT and fibroadenoma. Strict histologic assessment of a combination of histologic features with classification can help to achieve the correct diagnosis and provide useful clinical information. The genomic landscapes of PT generated from genomic sequencing provide insights into the molecular pathogenesis of PT and help to improve diagnostic accuracy and identify potential drug targets in malignant PT.

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“…Our laboratory and other investigators have recently found that EZH2 regulates breast cancer stem cells [10,13]. The aldehyde dehydrogenase I enzyme (ALDH1), a biomarker of normal and malignant human mammary stem cells [14,15], has been recently detected in association with mesenchymal stem cell markers in a group of malignant PTs [16]. However, the expression of EZH2 in PT has not been previously investigated, and the potential diagnostic and clinical significance of EZH2 and ALDH1 expression in a spectrum of benign, borderline, and malignant PTs is unknown.…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Liss

Chung

et al. 2016

Breast Cancer Res Treat

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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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Malignant phyllodes tumors display mesenchymal stem cell features and aldehyde dehydrogenase/disialoganglioside identify their tumor stem cells

Cited by 38 publications

References 39 publications

Heterologous Liposarcomatous Differentiation in Malignant Phyllodes Tumor is Histologically Similar but Immunohistochemically and Molecularly Distinct from Well-differentiated Liposarcoma of Soft Tissue

Heterologous Liposarcomatous Differentiation in Malignant Phyllodes Tumor is Histologically Similar but Immunohistochemically and Molecularly Distinct from Well-differentiated Liposarcoma of Soft Tissue

Phyllodes Tumor of the Breast: Histopathologic Features, Differential Diagnosis, and Molecular/Genetic Updates

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

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