Prognostic significance of cathepsin-D expression in node-positive breast carcinoma: an immunohistochemical study.
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.
Têtu
B
B
Department of Pathology, Université Laval, L'Hôtel-Dieu de Québec, Canada.
Brisson
J
J
Côté
C
C
Brisson
S
S
Potvin
D
D
Roberge
N
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D002277:Carcinoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D002402:Cathepsin D / Q000032:analysis*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
D002402:Cathepsin D