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Cathepsin-D in Human Encjometrium: Induction by Progesterone and Potential Value as a Tumor Marker^*

Institut National de la Santé et de la Recherche Médicale, Unité Hormones et Cancer (U148) (T.M., P.M., H.R.) 34090 Montpellier
Laboratoire de Biologie Cellulaire et Hormonale (T.M., J-P.B., H.R.) and Service de Gynécologie Obstétrique (F.L.), Maternité, and Laboratoire d'Anatomie Pathologique Centre Gui de Chauliac (A.P.) CHR, 34059 Montpellier, France

Address all correspondence and requests for reprints to: Dr. Henri Rochefort, Institut National de la Santé et de la Recherche Medicale, Unité Hormones et Cancer (U148), 60 rue de Navacelles, 34090 Montpellier, France.

Using an immunoenzymatic assay, cathepsin-D concentrations were measured in the cytosol of human endometrium biopsies. The level of cathepsin-D was higher in the luteal phase than in the follicular phase (P < 0.01), suggesting increased accumulation by progesterone. Induction by progestin was confirmed by immunoprecipitation of cathepsin-D from a lysate of epithelial endometrial cells previously treated in primary culture with R5020 (10 nM); estradiol (10 nM) had no effect. Immunohistochemistry showed that cathepsin-D is mainly localized in the epithelium and that its level is higher in the luteal phase. The plasma level of cathepsin-D was stable during the menstrual cycle, ranging between 2.5-10 pmol/mL, but increased slightly during pregnancy. The mean level of cathepsin-D was higher in 19 endometrial carcinoma than in 20 normal endometrium, but was not correlated with steroid receptor status. However, using 15 pmol/mg protein as a cut-off level, the cathepsin-D status (high or low) was correlated with the degree of myometrial invasion (one third) by adenocarcinoma cells, whereas steroid receptor status was not.

We conclude that cathepsin-D is induced by progesterone in human endometrium, as it is in normal rat uterus, and we suggest that a low concentration of cathepsin-D in the cytosol of endometrial adenocarcinoma may indicate a favorable prognosis, since it is correlated with low myometrial invasion.

^* This work was supported by the Institut National de la Santé et de la Recherche Médicale, the University of Montpellier I, the Association pour la Recherche sur le Cancer, and the Fédération Nationale des Centres de Lutte contre le Cancer.

Received February 6, 1989.

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