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Department of Surgical Sciences (F.P., S.L.), Chair of Obstetrics and Gynecology, University of Udine, Udine, Italy; Département de Médecine (C.L., P.P.), Département d’Anatomie Pathologique (J.C.S.) and Département de Biologie Clinique (J.M.B.), Institut Gustave-Roussy, Villejuif; and Unité de Recherches sur l’Endocrinologie du Développement, INSERM U493 (R.R.), Ecole Normale Supérieure, Montrouge, France.
Address correspondence to: Jean-Michel Bidart, Department of Clinical Biology, Institut Gustave-Roussy, Villejuif, France.
Abstract
Both experimental and clinical studies suggest that inhibin plays a critical role in the development of granulosa cell tumors (GCT), a subgroup of malignant ovarian tumors. Inhibin has been proposed as a biological marker for the follow-up of patients bearing these particular tumors. Hitherto, there is no general agreement on the molecular form(s) of the inhibin family that are secreted by malignant granulosa cells. Using specific and sensitive immunoassays for activin A and for inhibins A and B, we investigated the production of these molecules in patients with either an adult GCT (n = 13) or an epithelial ovarian cancer (n = 11). Results showed that serum activin A level was increased in all patients, independently of their clinical status (progressive disease or remission) in comparison to that observed in the healthy pre- and postmenopausal women. Most of the patients also presented a moderate increase in serum inhibin A level compared to that in controls. Only one of eight patients with a progressive granulosa cell tumor had a high value of serum inhibin A. In contrast, serum inhibin B was dramatically increased in eight of nine patients with a granulosa cell tumor and its level correlated with the clinical status of the patients. No correlation was found between the level of serum inhibin B and that of serum antimüllerian hormone, a recently described specific and reliable marker for GCT. None of the patients with an epithelial ovarian cancer presented an increase of serum inhibin B. These observations demonstrate that inhibin B is the major molecular form of the inhibin family proteins produced by malignant granulosa cells.
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