Background: An increased cathepsin D (cath-D) level in breast carcinoma cytosol has been proposed as a prognostic parameter. However, no increase had been previously detected in serum when assaying total cath-D concentration.
Methods: The authors compared 2 radioimmunoassays of total 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 serum of 18 of the 30 patients with metastatic breast carcinoma. No increase was observed in any of the patients with nonmetastatic disease compared with healthy women. Moreover, the level of pro-cath-D was often superior to that of total cath-D in the same patients, suggesting that the total cath-D assay in serum underestimates the actual concentration of pro-cath-D. This is not believed to be due to the masking of cath-D with the circulating mannose-6-phosphate/insulin-like growth factor II receptor because the purified receptor did not interfere in the binding of the monoclonal antibodies used in the assay to cath-D.
Conclusions: An increased level of cath-D in the serum of breast carcinoma patients is a late event observed only in patients with metastatic disease. This increased circulating level is more likely due to increased secretion of the proenzyme rather than to tumor cell lysis.