Abstract
The prognostic significance of cathepsin‐D expression was evaluated by immunohistochemistry in 638 node‐positive breast carcinomas diagnosed between 1980 and 1986. A minimum of 2.5 years of follow‐up was available for each patient (maximum: 9.5 years). Cathepsin‐D expression was assessed separately both in cancer and in stromal cells using a commercially available polyclonal antibody. While cancer‐cell immunostaining was not associated with prognosis, positive staining of stromal elements was related to shorter metastasis‐free survival. The difference in distant metastasis‐free survival between positive and negative expressors was greatest in the sub‐group of patients submitted to adjuvant chemotherapy, with a hazard ratio for occurrence of distant metastasis of 1.76 by multivariate analysis, but was lowest for those receiving hormone therapy. Cathepsin‐D expression by stromal cells was related to HER‐2/ neu oncoprotein expression, HSP‐27 expression, poor nuclear grade, aneuploidy, and absence of estrogen and progesterone receptors. No association was found with the number of involved lymph nodes, tumor size, age, histologic grade, S‐phase fraction, or vascular invasion. Our study suggests that cathepsin‐D expression by stromal cells (and not by cancer cells) affects the prognosis of breast cancer, that stromal cells probably play a key role in local invasion and metastatic dissemination of the tumor, and that the prognostic significance of cathepsin‐D expression may vary according to the type of adjuvant therapy.