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Expression of CAF-Related Proteins Is Associated with Histologic Grade of Breast Phyllodes Tumor

 HyeMin Kim  ;  Yu Kyung Lee  ;  Ja Seung Koo 
 DISEASE MARKERS, Vol.2016 : 4218989, 2016 
Journal Title
Issue Date
Adult ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism* ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism* ; Breast Neoplasms/pathology ; Female ; Gelatinases/genetics ; Gelatinases/metabolism* ; Humans ; Membrane Proteins/genetics ; Membrane Proteins/metabolism* ; Middle Aged ; Neoplasm Metastasis ; Phyllodes Tumor/genetics ; Phyllodes Tumor/metabolism* ; Phyllodes Tumor/pathology ; Receptor, Platelet-Derived Growth Factor alpha/genetics ; Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Receptor, Platelet-Derived Growth Factor beta/genetics ; Receptor, Platelet-Derived Growth Factor beta/metabolism* ; Serine Endopeptidases/genetics ; Serine Endopeptidases/metabolism* ; Stromal Cells/metabolism ; Stromal Cells/pathology
Purpose. The purpose of this study was to investigate the expression of cancer-associated fibroblast- (CAF-) related proteins and the implications in breast phyllodes tumor (PT). Methods. Tissue microarrays of 194 PT cases (151 benign PT, 27 borderline PT, and 16 malignant PT) were constructed. We performed immunohistochemical staining for CAF-related proteins (podoplanin, prolyl 4-hydroxylase, FAPα, S100A4, PDGFR α/β, and NG2) and analyzed the results according to clinicopathologic parameters. Results. Expression of PDGFRα and PDGFRβ in the stromal component increased with increasing histologic grade of PT (p = 0.003 and p = 0.034, resp.). Among clinicopathologic parameters, only expression of FAPα in stroma was associated with distant metastasis (p = 0.002). In univariate analysis, stromal expression of PDGFRα was associated with shorter overall survival (p = 0.002). In Cox multivariate analysis, stromal overgrowth and PDGFRα stromal positivity were associated with shorter overall survival (p = 0.006 and p = 0.050, resp.). Furthermore, expression of PDGFRβ in stroma was associated with shorter overall survival in patients with malignant PT (p = 0.041). Conclusion. Stromal expression of PDGFRα and PDGFRβ increased with increasing histologic grade of PT. In addition, PDGFR stromal positivity was associated with shorter overall survival. These results suggest that CAFs are associated with breast PT progression.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Koo, Ja Seung(구자승) ORCID logo https://orcid.org/0000-0003-4546-4709
Kim, Hye Min(김혜민) ORCID logo https://orcid.org/0000-0002-2899-9480
Lee, Yu Kyung(이유경)
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