CD34, CD117, and Ki-67 Expression in Phyllodes Tumor of the Breast: An Immunohistochemical Study of 33 Cases

Noronha, Yvonne Saldanha; Raza, Anwar; Hutchins, Brian; Chase, Donald R.; Garberoglio, Carlos A.; Chu, Peiguo; Weiss, Lawrence M.; Wang, Jun

doi:10.1177/1066896910382009

Cited by 46 publications

(34 citation statements)

References 22 publications

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“…First, we tested the expression of Ki67 and myofibroblast markers, including a-SMA, fibroblast activation protein (FAP), and stromal cell-derived factor-1 (SDF-1), in paraffin-embedded phyllodes tumor samples by IHC. Similar to previous studies (20)(21)(22), the expression of Ki67 increased significantly with phyllodes tumors grade (Fig. 1A).…”

Section: Resultssupporting

confidence: 80%

miR-21 Induces Myofibroblast Differentiation and Promotes the Malignant Progression of Breast Phyllodes Tumors

Gong

Nie

et al. 2014

Cancer Research

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Phyllodes tumors of breast, even histologically diagnosed as benign, can recur locally and have metastatic potential. Histologic markers only have limited value in predicting the clinical behavior of phyllodes tumors. It remains unknown what drives the malignant progression of phyllodes tumors. We found that the expression of myofibroblast markers, a-smooth muscle actin (a-SMA), fibroblast activation protein (FAP), and stromal cell-derived factor-1 (SDF-1), is progressively increased in the malignant progression of phyllodes tumors. Microarray showed that miR-21 was one of the most significantly upregulated microRNAs in malignant phyllodes tumors compared with benign phyllodes tumors. In addition, increased miR-21 expression was primarily localized to a-SMA-positive myofibroblasts. More importantly, a-SMA and miR-21 are independent predictors of recurrence and metastasis, with their predictive value of recurrence better than histologic grading. Furthermore, miR-21 mimics promoted, whereas miR-21 antisense oligos inhibited, the expression of a-SMA, FAP, and SDF-1, as well as the proliferation and invasion of primary stromal cells of phyllodes tumors. The ability of miR-21 to induce myofibroblast differentiation was mediated by its regulation on Smad7 and PTEN, which regulate the migration and proliferation, respectively. In breast phyllodes tumor xenografts, miR-21 accelerated tumor growth, induced myofibroblast differentiation, and promoted metastasis. This study suggests an important role of myofibroblast differentiation in the malignant progression of phyllodes tumors that is driven by increased miR-21. Cancer Res; 74(16); 4341-52. Ó2014 AACR.

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Section: Resultssupporting

confidence: 80%

miR-21 Induces Myofibroblast Differentiation and Promotes the Malignant Progression of Breast Phyllodes Tumors

Gong

Nie

et al. 2014

Cancer Research

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“…Although the data on increased stromal cellularity are inconsistent, many studies have found that subepithelial condensation of stromal cells is a common feature of PT and may be the best predictor of PT in core biopsies. 16 Stromal overgrowth, defined as a stromal proliferation without accompanying epithelial elements in at least 1 lowpower field (34), is a feature of PT. However, stromal overgrowth is absent in benign PT.…”

Section: 16mentioning

confidence: 99%

“…Studies have shown that p53, Ki67, CD117, 34,35 EGFR, 36 p16, 37 and VEGF 38 (being the lowest in benign PT and the highest in malignant PT) are associated with histologic grades of PT, but none has been proven to be clinically useful. Among these markers, p53 expression and Ki67 index were reported in some studies 39,40 to be significantly associated with disease-free and overall survivals, but other studies 41,42 found no association with recurrence or clinical behavior.…”

Section: Molecular/genetic Featuresmentioning

confidence: 99%

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

Zhang

Kleer

2016

Archives of Pathology &Amp; Laboratory Medicine

200

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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“…6,7 Several other reports have also shown an association of CD117 protein expression with increasing grade, 11,16 with a few detailing preferential expression of CD117 in the malignant phenotype. 6,7,12,17,18 However, there were also several groups that indicated no association between CD117 expression and tumor grade. 8,9,19 In this study, we observed CD117 expression to be associated with borderline and malignant grade tumors.…”

Section: Discussionmentioning

confidence: 99%

CD117 expression in breast phyllodes tumors correlates with adverse pathologic parameters and reduced survival

et al. 2015

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and 5 Duke-NUS Graduate Medical School, Singapore CD117 (c-kit) is a type III receptor tyrosine kinase encoded by the KIT gene. Deregulation of expression and mutations in the gene are implicated in various tumors. Reports of CD117 expression in phyllodes tumors have been controversial. We aim to investigate the protein expression of CD117 and mutations in the KIT gene in phyllodes tumors, and correlate the findings with pathological parameters and clinical outcome. A total of 272 cases were included in this study. CD117 expression was investigated by immunohistochemistry on tissue microarray sections. Toluidine blue staining was performed to indicate mast cells. Overall, 28 (10%) cases were CD117 positive. CD117 expression was significantly associated with tumor grade (Po0.001), increased stromal hypercellularity (P ¼ 0.003), stromal atypia (P ¼ 0.01), and stromal mitotic activity (Po0.001), permeative microscopic margins (P ¼ 0.002), and presence of hemorrhage (P ¼ 0.001). Expression was also associated with poorer overall survival (P ¼ 0.003). Nineteen cases were further selected for mutation screening through the Affymetrix OncoScan platform. No mutation of the KIT gene was found. Despite a lack of mutations in the KIT gene, CD117 protein expression is associated with unfavorable pathological parameters and poorer prognosis, suggesting an underlying role in the biology of phyllodes tumors.

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CD34, CD117, and Ki-67 Expression in Phyllodes Tumor of the Breast: An Immunohistochemical Study of 33 Cases

Cited by 46 publications

References 22 publications

miR-21 Induces Myofibroblast Differentiation and Promotes the Malignant Progression of Breast Phyllodes Tumors

miR-21 Induces Myofibroblast Differentiation and Promotes the Malignant Progression of Breast Phyllodes Tumors

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

CD117 expression in breast phyllodes tumors correlates with adverse pathologic parameters and reduced survival

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