Cathepsin D expression by cancer and stromal cells in breast cancer: an immunohistochemical study of 1348 cases

This study was aimed at investigating the influence of cathepsin D (CD) exp ression by cancer cells and stromal cells on breast cancer prognosis. This is a study of 1348 node-positive (NPBC) and node-negative (NNBC) breast can cers diagnosed between 1980 and 1986 and with a minimum follow-up of 5.2 ye ars. CD expression was assessed by immunohistochemistry on archival materia l using a polyclonal antibody. The expression by cancer and stromal cells w as assessed separately and correlated with distant metastasis free (DMFS) a nd overall survival (OS). Cancer cells expressed CD (more than 10% cells ex pressing CD) in 38.9% of cases and reactive stromal cells in 43.6%. CD expr ession by reactive stromal cells, and not cancer cells, correlated with sev eral factors of poor prognosis by cancer cells. A strong association was al so found with expression of other proteases (stromelysin-3, gelatinase A, a nd urokinase Plasminogen Activator) by these same reactive stromal cells. C D expression by cancer cells did not predict DMFS or OS but, by univariate analysis, CD expression by reactive stromal cells was associated with earli er recurrence and shorter survival in NNBC (p = 0.0425) and NPBC patients s ubmitted to adjuvant chemotherapy (p = 0.0234). However, CD expression by r eactive stromal cells remained a significant predictor of recurrence by mul tivariate analyses only in a subgroup of NPBC submitted to adjuvant chemoth erapy. Overall, those data support the concept that proteases produced by r eactive stromal cells are under cancer cell stimulation and that CD by stro mal cells, and not cancer cells, influences the prognosis, but only in a su bgroup of patients with breast cancer.