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 prognostic factor in predicting relapse and metastasis. Nevertheless, since 30% of node-negative tumours also relapse, it is necessary to develop other independent prognostic factors. Oncogene amplification and overexpression as well as the level of cathepsin-D have been proposed as additional prognostic factors. Recent studies suggest that the acidic lysosomal proteinase cath-D, present in all cells and known to be secreted in breast cancer cells, may be implicated in the process of tumour 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 showed a positive correlation with c-myc amplification (P = 0.01) or overexpression (P = 0.02). In contrast, no correlation 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 node invasiveness, steroid receptors, grade and menopausal status. Nevertheless, a weak correlation was found between cath-D levels and tumour status (P = 0.05). In conclusion, in breast cancer, a high cytosolic cath-D concentration is more frequent in tumours with c-myc amplification and overexpression but is dissociated from c-erb-B-2 amplification or overexpression, suggesting that the determination of cath-D, as well as the latter two markers, will have an additional prognostic value.
Scorilas
A
A
Department of Biochemistry, G. Papanikolaou Research Center of Oncology, Hellenic Anticancer Institute, Athens, Greece.
Yotis
J
J
Gouriotis
D
D
Keramopoulos
A
A
Ampela
K
K
Trangas
T
T
Talieri
M
M
D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology; D002402:Cathepsin D / Q000032:analysis*; D003600:Cytosol / Q000737:chemistry; D066246:ErbB Receptors / Q000032:analysis*; D005260:Female; D005784:Gene Amplification; D016259:Genes, myc; D006801:Humans; D015592:Immunoradiometric Assay; D008207:Lymphatic Metastasis; D008593:Menopause; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D018719:Erb-b2 Receptor Tyrosine Kinases; D011987:Receptors, Steroid / Q000032:analysis
D002402:Cathepsin D; D066246:ErbB Receptors; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011987:Receptors, Steroid