Association between high concentrations of Mr 52,000 cathepsin D and poor prognosis in primary human breast cancer.
The Mr 52,000 cathepsin D is the precursor of a lysosomal protease secreted in excess by breast cancer cells. This protease can degrade extracellular matrices and proteoglycans and is induced by estrogens in estrogen receptor-positive breast cancer cell lines. In a 4- to 6-yr retrospective cohort study, the concentration of the total cathepsin D (precursor plus intermediate and mature chains) was assayed in cytosols of primary tumors from 242 pre/perimenopausal and 154 postmenopausal breast cancer patients in a solid-phase immunoassay using two specific monoclonal antibodies. Patients were initially divided into groups with low, intermediate, or high concentrations of cathepsin D corresponding to the quartiles of the overall distribution. Using these groupings, the level of Mr 52,000 cathepsin D was not significantly associated with the recognized prognostic factors of age, lymph node involvement, tumor size, and/or grade of anaplasia. A significant association was found between cathepsin D concentrations and estrogen receptor status only among pre/perimenopausal patients. Receptor-positive tumors (greater than or equal to 10 fmol of estrogen receptor/mg of cytosol protein) had a significantly greater proportion of patients with high Mr 52,000 cathepsin D concentrations. Patients with high Mr 52,000 cathepsin D concentrations (greater than 78 pmol/mg for pre/perimenopausal and greater than 24 for postmenopausal patients) have shorter recurrence-free survival (P = 0.06 for pre/peri- and P = 0.039 for postmenopausal patients) and have a trend toward shorter overall survival (P = 0.30 and P = 0.089 for pre/peri- and postmenopausal groups, respectively). In multivariate analysis, Mr 52,000 cathepsin D status was found to be an independent prognostic factor for recurrence-free survival of about the same import as lymph node status for both menopausal groups. This first retrospective study demonstrates that the level of Mr 52,000 cathepsin D in cytosol of primary breast cancer biopsies is an independent prognostic factor in predicting relapses in both pre/peri- and postmenopausal patients.
Thorpe
S M
SM
University Department of Clinical Physiology and Nuclear Medicine, Finsen Institute, Rigshospitalet, Copenhagen, Denmark.
Rochefort
H
H
Garcia
M
M
Freiss
G
G
Christensen
I J
IJ
Khalaf
S
S
Paolucci
F
F
Pau
B
B
Rasmussen
B B
BB
Rose
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000032:analysis / Q000175:diagnosis* / Q000201:enzymology / Q000473:pathology; D002402:Cathepsin D / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008593:Menopause; D008875:Middle Aged; D008970:Molecular Weight; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis
D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D002402:Cathepsin D