Relationships of Na+ and K+ concentrations to GRP,CGRP, and calcitonin immunoreactivities and Na+,K+-ATPase (NKA) inhibitory activity in human breast cyst fluid

Background: Although the etiology of gross cystic disease of the breast is unknown, elevated cyst concentrations of potassium (K⁺) (>60 mM/L) may be related to symptoms. The purpose ofthis study was to clarify the mechanism(s) of K⁺ accumulation in breast cysts. Methods: We assayed cyst fluids for factors known to exert effects on K⁺ transport, namely, endogenous digitalis-like inhibitors of Na⁺,K⁺-ATPase (NKA) and the neuropeptides gastrin-releasing peptide (GRP), calcitonin (CT), and calcitonin gene-related peptide (CGRP). Results: Cyst fluid K⁺ was directly correlated with cyst volume, cyst NKA inhibitory activity (in ouabain equivalents), and cyst concentrations of calcitonin, GRP, and CGRP. Cyst fluid Na⁺ was inversely correlated with cyst fluid K⁺, cyst NKA inhibitory activity, cyst volume, and cyst fluid concentrations of calcitonin, GRP, and CGRP. NKA inhibitory activity correlated directly with GRP and CGRP. Immunocytochemistry localized GRP to breast cyst lining cells and areas of ductal and lobular epithelial hyperplasia in biopsies of 15 of 15 cysts and in 5 of 5 breast carcinomas, but not in (0 of 5) normal breast biopsies. Specificity of GRP staining was demonstrated by total abolition of reactivity after adsorption with synthetic GRP, but not after adsorption with synthetic substance P, neurokinin A, or neurokinin B. Conclusions: We conclude that both the concentrations of endogenous digitalis-like factors and the neuropeptides calcitonin, GRP, and CGRP in human breast cyst fluids are related to the concentrations of K⁺ and Na⁺ in breast cysts and to cyst volume.