CATHEPSIN-D AND C-ERB-B-2 HAVE AN ADDITIVE PROGNOSTIC VALUE FOR BREAST-CANCER PATIENTS

In breast cancer, axillary lymph node invasiveness is the major progno stic factor in predicting I elapse and metastasis. Nevertheless, since 30% of node-negative tumours also relapse, it is necessary to develop other independent prognostic factors. Oncogene amplification and over expression as well as the level of cathepsin-D have been proposed as a dditional prognostic factors. Recent studies suggest that the acidic l ysosomal proteinase cath-D, present in all cells and known to be secre ted in breast cancer cells, may be implicated in the process of turnou t invasion and metastasis. We have compared the cytosolic cath-D level with the amplification and the overexpression of the oncogenes c-myc and c-erb-b-2 in 62 breast carcinomas (52 primary and 10 metastatic). Using a cut-off level of 60 pmol/mg protein, the status of cath-D show ed a positive correlation with c-myc amplification (P=0.01) or overexp ression (P=0.02). In contrast, no col relation was found between cath- D and c-erb-B-2 amplification or overexpression. Also, no correlation was found between cath-D and established prognostic factors such as no de invasiveness, steroid receptors, grade and menopausal status. Never theless, a weak correlation was found between cath-D levels and tumour status (P=0.05). In conclusion, in breast cancer, a high cytosolic ca th-D concentration is more frequent in tumours with c-myc amplificatio n and overexpression but is dissociated from c-erb-B-2 amplification o r overexpression, suggesting that the determination of cath-D, as well as the latter two markers, will have an. additional prognostic value.