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Immunoenzymatic Assay of M_r 52,000 Cathepsin D in 182 Breast Cancer Cytosols: Low Correlation with Other Prognostic Parameters¹

INSERM U 148, Unité d'Endocrinologie Cellulaire et Moléculaire, 60 Rue de Navacelles, 34100 Montpellier [T. M., M. G., G. F., J. D., Hen. R.]; Laboratoire de Biochimie Cellulaire et Hormonale, Maternité, 13 Avenue du Professeur Grasset, 34060 Montpellier [T. M., S. K., M. B., Hen. R.]; Centre Val d'Aurelle Paul Lamarque, 34094 Montpellier [J. S., H. P.]; and Sanofi-Recherche, Laboratoire Immuno Diagnostic, Rue du Professeur Joseph Blayac, 34082 Montpellier [Hen. R., F. P., B. P.], France

The M_r 52,000 cathepsin-D-like protease induced by estrogens in MCF7 human breast cells was assayed in 182 primary breast cancer cytosols prepared for receptor assays from pre- and post-menopausal patients. Using two solid-phase sandwich immunoenzymatic assays, we quantified the total M_r 52,000 cathepsin D (52K-cath-D) (the M_r 52,000 precursor protein and its M_r 48,000 and 34,000 processed forms) and the M_r 52,000 precursor alone. The value of total 52K-cath-D varied between 3 and 165 pmol/mg protein and the proportion of the precursor varied from 0 to 28% of total 52K-cath-D. There was no correlation between the concentrations of 52K-cath-D and estrogen receptor, but the estrogen receptor status (> or <10 fmol/mg protein) was correlated to the 52K-cath-D status (> or <15 pmol/mg protein) according to the x² test (P < 0.001). The correlation with progesterone receptor concentrations and status was low (r = 0.43) and absent, respectively. There was no correlation with Scarff and Bloom stages, tumor size, or patient's age. The percentage of patients with invaded lymph nodes was significantly higher (80%) in the subgroup with the highest total 52K-cath-D levels (42 pmol/mg protein), representing only 12% of the population but not in the total population.

On the basis of this prospective study, before clinical follow-up can be evaluated, we conclude that in the total population examined, the 52K-cath-D concentration was only correlated with estrogen receptor status, but not with any other prognostic parameter.

¹ This work was supported by the Institut National de la Santé et de la Recherche Médicale, Grant INSERM-SANOFI 81039-3, the University of Montpellier I, and the Association pour la Recherche sur le Cancer and the Pole Régional de Génie Biologique et Médical.

² To whom requests for reprints should be addressed.

Received 2/ 6/87. Revised 6/26/87. Revised 9/23/87. Accepted 10/ 1/87.