title: Expression of CAF-Related Proteins Is Associated with Histologic Grade of Breast Phyllodes Tumor.
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, PDGFRα/β, and NG2) and analyzed the results according to clinicopathologic parameters.Results. Expression of PDGFRαand PDGFRβin the stromal component increased with increasing histologic grade of PT (p= 0.003 andp= 0.034, resp.). Among clinicopathologic parameters, only expression of FAPαin stroma was associated with distant metastasis (p= 0.002). In univariate analysis, stromal expression of PDGFRαwas associated with shorter overall survival (p= 0.002). In Cox multivariate analysis, stromal overgrowth and PDGFRαstromal positivity were associated with shorter overall survival (p= 0.006 andp= 0.050, resp.). Furthermore, expression of PDGFRβin stroma was associated with shorter overall survival in patients with malignant PT (p= 0.041).Conclusion. Stromal expression of PDGFRαand PDGFRβincreased 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.
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hye Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yu Kyung
authors.initials: YK
authors.lastname: Lee
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ja Seung
authors.identifier: 0000-0003-4546-4709
authors.initials: JS
authors.lastname: Koo
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010450:Endopeptidases; D005260:Female; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D003557:Phyllodes Tumor / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D014408:Biomarkers, Tumor; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha