PROGNOSTIC INDICATORS FOR EARLY-STAGE BREAST-CARCINOMA .2. VALUE OF CATHEPSIN-D EXPRESSION, DETECTED BY IMMUNOCYTOCHEMISTRY - A MULTIPARAMETRIC STUDY

Cathepsin D is a lysosomal aspartyl protease which seems to be involved in invasiveness and metastasis in breast carcinoma. Cathepsin D expression detected by immunocytochemistry is a new potentially useful prognostic marker. Additional research is warranted because: (i) few immunocytochemical studies have been performed to correlate cathepsin D expression and prognosis; (ii) a consensus has not yet been achieved on methodology and quality control issues; (iii) the association between cathepsin D expression and other new biological markers is poorly known and (iv) few studies have assessed whether cathepsin D expression is an independent prognostic marker when compared with other biological and clinico-pathological features using multivariate analysis. This study was undertaken in the same series of 165 stage I-II breast cancer patients (median follow-up of 5 years) already reported (Int J Oncol 4: 155-162, 1994) in whom cathepsin D was assessed using the D7E3 monoclonal antibody by immunocytochemistry in frozen specimens, using a standard peroxidase-antiperoxidase complex method. Cathepsin D was compared with another 7 biological markers, as well as with the conventional clinico-pathological features. Forty-two carcinomas of the 165 analyzed (25.5%) were cathepsin D-positive. This marker was significantly associated with c-erbB-2 expression (p=0.004) and tumour vascularization (p=0.02). Yet, a weak association was observed between cathepsin D and S-phase fraction (p=0.06). In univariate analysis cathepsin D was significantly associated both with relapse-free survival (p<0.01) and overall survival (p=0.02). In multivariate analysis, for relapse-free survival the variables cathepsin D/tumour vascularization, as well as S-phase fraction and EGFR, were significant and independent. For overall survival the variables cathepsin D/c-erbB-2 protein, as well as tumour vascularization and S-phase fraction were significant and independent. Immunocytochemical determination of cathepsin D, using the D7E3 antibody, seems to be a useful prognostic tool in early-stage breast cancer. In particular, cathepsin D adds prognostic information to tumour vascularization (in predicting relapse-free survival) and to c-erbB-2 expression (in predicting overall survival).