Characterization of inhibin immunoreactivity in post‐menopausal women with ovarian tumours

Abstract

We have previously reported elevated serum immunoreactive inhibin (INH) levels in patients with ovarian malignancies, particularly granulosa cell and mucinous tumours. The present study was designed to compare INH measurements using a heterologous radioimmunoassay with cross-reactivity for inhibin alpha-subunit derived peptides with measurements obtained using a new ELISA specific for dimeric inhibin-A. It was hypothesized that granulosa cell tumours may secrete significant quantities of inhibin-A whereas mucinous tumours were unlikely to do so because of the lack of a relation between INH and FSH measurements in the latter group. Serum samples obtained from women found to have ovarian cancer were assayed using the heterologous radioimmunoassay (the Monash assay) and using an ELISA specific for dimeric inhibin (the Groome assay) and the results were compared. Samples for assay were available from 69 normal post-menopausal control women, 12 patients with mucinous tumours of the ovary, 26 with serous tumours, 7 with granulosa cell tumours and 8 with various other ovarian tumours. Patients were post-menopausal or had been subjected to bilateral oophorectomy at the time these samples were collected. The Monash and Groome assays were carried out as described previously. The upper limit of normal for post-menopausal women in the Monash assay was 122 U/l and for the Groome assay was calculated to be 32 ng/l. Among the 69 normal subjects, 4 were found to have elevated inhibin levels using the Monash RIA (133-190 U/l) and 4 were found to have elevated levels in the Groome ELISA (45.5-55.3 ng/l). Among 12 patients with mucinous tumours, 10 (83%) had elevated inhibin levels using the Monash assay but only 3 (25%) had elevated levels with the Groome assay (P < 0.005). Among 26 with serous tumours, 15 (58%) had elevated levels in the Monash assay but only 1 (4%) in the Groome assay (P < 0.001). Among 7 samples from patients with granulosa cell tumours, 100% were elevated in the Monash assay and 71% in the Groome assay (NS, non-significant). In a miscellaneous group of tumours all 8 had elevated levels in the Monash assay and 2 in the Groome assay (P < 0.001). It was concluded that in normal postmenopausal subjects, INH is generally undetectable or present at low levels, consistent with the loss of ovarian function. The majority of granulosa cell tumours appear to secrete significant amounts of dimeric inhibin-A, whereas mucinous tumours secrete predominantly other forms of INH, presumably related to the alpha-subunit. Serous tumours may also secrete inhibin-related peptides but not dimeric inhibin-A. The nature of the inhibin related peptides produced by epithelial ovarian cancers remains to be characterized.