OVEREXPRESSION OF PDGF RECEPTOR-BETA IN DERMAL FIBROBLASTS OF LYMPHANGITIC POST RADIOTHERAPY RELAPSES OF BREAST-CARCINOMA

Lymphangitic relapses of breast cancer, initiating in the area irradia ted for conservative treatment, are rare but not uncommon. Clinical an d physiopathological observations such as intense fibrotic swelling 'e n cuirasse' of the lymphangitic area suggest cooperative stromal-epith elial interactions which promote and/or sustain the growth of tumour c ells. In order to assess the role of paracrine interactions between ir radiated stromal cells and tumour cells in this clinical type of relap se, we have performed a semi-quantitative immunohistochemical study of the PDGF Receptor beta (PDGFR beta) on skin biopsies obtained from 36 patients and we have tested the sensitivity to its specific ligand, t he platelet derived growth factor homodimer BE (PDGF BE) of dermal fib roblasts in culture from biopsies of six of these patients. We observe d a consistently increased immunoreactivity of PDGFR beta in the derma l fibroblasts of irradiated lymphangitic skin, when compared to irradi ated skin without lymphangitic recurrence (P < 0.0001). For all patien ts tested, the stimulatory effects of PDGF BE on [H-3]thymidine incorp oration and on cell growth in culture was significantly greater on fib roblasts from the irradiated field than on those from a non-irradiated field or from the skin of healthy donors. PDGF BE immunoreactivity wa s 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 exte nsive inflammatory skin recurrence.