Platelet-derived growth factor expression in phyllodes tumors and fibroadenomas of the breast

Abstract

The development of normal breast tissue and the pathogenesis of various tumors are influenced by growth factor—mediated epithelial-stromal interactions. Similar interactions may occur in fibroepithelial breast tumors. We have studied the expression of platelet-derived growth factor (PDGF) and PDGF beta receptor (PDGFRβ) in 46 phyllodes tumors (18 benign, 15 borderline, 13 malignant), 11 fibroadenomas, and 6 samples of normal breast. There was neoplastic stromal cell positivity for PDGFRβ in almost 50% of phyllodes tumors and for PDGF in 24%. Both were associated with prominent nuclear pleomorphism ( P < .01), PDGF with high grade ( P < .01), and a higher mean Ki-67 labeling index ( P = .013), and PDGFRβ with conspicuous stromal overgrowth ( P < .01). Co-positivity for stromal PDGF and PDGFRβ was found in 15% of phyllodes tumors, and for epithelial PDGF and stromal PDGFRβ in 43%. Both types of co-positivity were associated with prominent nuclear pleomorphism and the latter type with conspicuous stromal overgrowth (all P < .01). Follow-up of 41 phyllodes tumors showed that disease-related death was associated with established histologic features of malignancy including mitotic count, stromal overgrowth, an infiltrative tumor margin, and nuclear pleomorphism. In addition, stromal PDGFRβ positivity ( P = .013) and epithelial PDGF/stromal PDGFRβ co-positivity ( P = .0075) were associated with disease-related death. Stromal PDGF and PDGFRβ expression in fibroadenomas was less common and less extensive ( P .05) than in phyllodes tumors. The results suggest that PDGF influences the pathogenesis of fibroepithelial breast tumors and that PDGF-dependent paracrine and autocrine mechanisms may operate. Also, it is possible that assessment of PDGF and PDGFRβ expression could contribute to the management of these tumors in the future. H UM P ATHOL 31:1214-1222.