INCREASED CATHEPSIN-D LEVEL IN THE SERUM OF PATIENTS WITH METASTATIC BREAST-CARCINOMA DETECTED WITH A SPECIFIC PRO-CATHEPSIN-D IMMUNOASSAY

BAGKGROUND. An increased cathepsin D (cath-D) level in breast carcinom a cytosol has been proposed as a prognostic parameter. However, no inc rease had been previously detected in serum when assaying total cath-D concentration. METHODS. The authors compared 2 radioimmunoassays of t otal cath-D and pro-cath-D in the serum of 3 groups of patients: those with metastatic breast carcinomas (n = 30), those with nonmetastatic breast carcinomas (n = 24), and healthy women (n = 21). RESULTS. There was a significant increase of total cath-D and pro-cath-D in the seru m of 18 of the 30 patients with metastatic breast carcinoma. No increa se was observed in any of the patients with nonmetastatic disease comp ared with healthy women. Moreover, the level of pro-cath-D was often s uperior to that of total cath-D in the siune patients, suggesting that the total cath-D assay in serum underestimates the actual concentrati on of pro-cath-D. This is not believed to be due to the masking of cat h-D with the circulating mannose-6-phosphate/insulin-like growth facto r II receptor because the purified receptor did not interfere in the b inding of the monoclonal antibodies used in the assay to cath-D. CONCL USIONS. An increased level of cath-D in the serum of breast carcinoma patients is a late went observed only in patients with metastatic dise ase. This increased circulating level is more likely due to increased secretion of the pro-enzyme rather than to tumor cell lysis. (C) 1997 American Cancer Society.