Endothelin-1, Endothelin-A- and Endothelin-B-receptor expression in preinvasive and invasive breast disease.

Endothelin-1 (ET-1) is overexpressed in breast carcinomas and influences via its receptors (ETAR and ETBR) transformation, differentiation and growth processes in the human breast, but little is known about the ET expression in breast cancer precursors. On this basis we evaluated the expression of ET-1, ETAR and ETBR in a series of breast carcinomas, ductal (DCIS) and lobular carcinoma in situ (LCIS) and normal breast tissue by immunohistochemical (IH) methods. IH staining of ET-1, ETAR and ETBR was performed in 88 invasive breast carcinomas, with adjacent carcinoma in situ and concomitant normal breast tissue. Moderate or strong cytoplasmic immunostaining was observed for ET-1 in 33.3%, for ETAR in 45.3% and for ETBR in 55.7% of invasive breast carcinomas. Comparative analysis of invasive cancer (CA), concomitant carcinoma in situ (CIS) and normal breast epithelium (NBE) revealed a stepwise increase of ET-1 and ETAR expression in the sequence NBE < CIS < CA. ETBR expression tended to be slightly higher in CIS than in CA (NBE versus CIS and NBE versus CA, for ETAR and ETBR, p<0.001, respectively; NBE versus CA for ET-1, p=0.035). Our data suggest that the expression of ET-1, ETAR and ETBR correlates with the acquisition of malignant potential and may be used as a prognostic indicator of aggressive behaviour and invasive potential of premalignant breast lesions.