CHARACTERIZATION OF INHIBIN IMMUNOREACTIVITY IN POSTMENOPAUSAL WOMEN WITH OVARIAN-TUMORS

BACKGROUND AND OBJECTIVE We have previously reported elevated serum im munoreactive inhibin (INH) levels in patients with ovarian malignancie s, particularly granulosa cell and mucinous tumours. The present study was designed to compare INH measurements using a heterologous radioim munoassay with cross-reactivity for inhibin alpha-subunit derived pept ides with measurements obtained using a new ELISA specific for dimeric Inhibin-A. It was hypothesized that granulosa cell tumours may secret e significant quantities of inhibin-A whereas mucinous tumours were un likely to do so because of the lack of a relation between INH and FSH measurements in the latter group. DESIGN Serum samples obtained from w omen found to have ovarian cancer were assayed using the heterologous radioimmunoassay (the Monash assay) and using an ELISA specific for di meric inhibin (the Groome assay) and the results were compared. PATIEN TS Samples for assay were available from 69 normal post-menopausal con trol women, 12 patients with mucinous tumours of the ovary, 26 with se rous tumours, 7 with granulosa cell tumours and 8 with various other o varian tumours. Patients were post-menopausal or had been subjected to bilateral oophorectomy at the time these samples were collected. MEAS UREMENTS The Monash and Groome assays were carried out as described pr eviously. The upper limit of normal for post-menopausal women in the M onash assay was 122 U/I and for the Groome assay was calculated to be 32 ng/l. RESULTS Among the 69 normal subjects, 4 were found to have el evated inhibin levels using the Monash RIA (133-190 U/I) and 4 were fo und to have elevated levels in the Groome ELISA (45.5-55.3 ng/l). Amon g 12 patients with mucinous tumours, 10 (83%) had elevated inhibin lev els using the Monash assay but only 3 (25%) had elevated levels with t he Groome assay (P < 0.005). Among 26 with serous tumours, 15 (58%) ha d elevated levels in the Monash assay but only 1 (4%) in the Groome as say (P < 0.001). Among 7 samples from patients with granulosa cell tum ours, 100% were elevated in the Monash assay and 71% in the Groome ass ay (NS, non-significant). In a miscellaneous group of tumours all 8 ha d elevated levels in the Monash assay and 2 in the Groome assay (P < 0 .001). CONCLUSIONS It was concluded that in normal postmenopausal subj ects, INH is generally undetectable or present at low levels, consiste nt with the lass of ovarian function. The majority of granulosa cell t umours appear to secrete significant amounts of dimeric inhibin-A, whe reas mucinous tumours secrete predominantly other forms of INN, presum ably related to the alpha-subunit. Serous tumours may also secrete inh ibin-related peptides but not dimeric inhibin-A. The nature of the inh ibin related peptides produced by epithelial ovarian cancers remains t o be characterized.