Overexpression of PDGF receptor β in dermal fibroblasts of lymphangitic post radiotherapy relapses of breast carcinoma

Lymphangitic relapses of breast cancer, initiating in the area irradiated for conservative treatment, are rare but not uncommon. Clinical and physiopathological observations such as intense fibrotic swelling ‘en cuirasse’ of the lymphangitic area suggest cooperative stromal-epithelial interactions which promote and/or sustain the growth of tumour cells. In order to assess the role of paracrine interactions between irradiated stromal cells and tumour cells in this clinical type of relapse, we have performed a semi-quantitative immunohistochemical study of the PDGF Receptor β (PDGFRβ) on skin biopsies obtained from 36 patients and we have tested the sensitivity to its specific ligand, the platelet derived growth factor homodimer BB (PDGF BB) of dermal fibroblasts in culture from biopsies of six of these patients. We observed a consistently increased immunoreactivity of PDGFRβ in the dermal fibroblasts of irradiated lymphangitic skin, when compared to irradiated skin without lymphangitic recurrence (P < 0.0001). For all patients tested, the stimulatory effects of PDGF BB on [3H]thymidine incorporation and on cell growth in culture was significantly greater on fibroblasts from the irradiated field than on those from a non-irradiated field or from the skin of healthy donors. PDGF BB immunoreactivity was observed in the malignant epithelial mammary cells infiltrating the dermis. This altered phenotype of the stromal component may contribute to relapse of breast carcinoma within the irradiated field as an extensive inflammatory skin recurrence.