Abstract
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.
Highlights
Progress in cancer research has increasingly revealed the clinical significance of the tumor microenvironment
Various proteins have been suggested as markers for cancerassociated fibroblasts (CAFs), including α-smooth muscle actin (SMA) [3], tenascin-C [4], chondroitin sulfate proteoglycan (NG2) [5], platelet-derived growth factor receptor (PDGFR)α/β [6], fibroblast activation protein (FAP) [7], podoplanin [8], prolyl 4-hydroxylase [9], and fibroblast-specific protein- (FSP-) 1 [5]
We investigated the expression of cancer-associated fibroblast- (CAF-)related proteins in breast phyllodes tumor (PT) according to histologic grade with the aim of identifying a new therapeutic target for PT
Summary
Progress in cancer research has increasingly revealed the clinical significance of the tumor microenvironment. CAFs are located near the cancer cells and have been reported to be involved in tumor initiation, tumor-stimulatory inflammation, metabolism, metastasis, drug response, and immune surveillance [2]. Despite their significant effect on cancer cells, the exact cell origin of CAFs is not completely understood and there is even controversy concerning the definition of CAF [1, 2]. CAFs have been suggested to show various functional subtypes that exhibit different characteristics [10], supporting the hypothesis that CAFs have various phenotypes
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