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 (PDGFRbeta) 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 PDGFRbeta 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 PDGFRbeta with conspicuous stromal overgrowth (P<.01). Co-positivity for stromal PDGF and PDGFRbeta was found in 15% of phyllodes tumors, and for epithelial PDGF and stromal PDGFRbeta 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 PDGFRbeta positivity (P =.013) and epithelial PDGF/stromal PDGFRbeta co-positivity (P =.0075) were associated with disease-related death. Stromal PDGF and PDGFRbeta 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 PDGFRbeta expression could contribute to the management of these tumors in the future.