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Characterization of Inhibin Forms and Their Measurement by an Inhibin -Subunit ELISA in Serum from Postmenopausal Women with Ovarian Cancer

Prince Henry’s Institute of Medical Research (D.M.R., T.S., E.P., H.G.B.), Clayton, Victoria 3168, Australia; Roche Products Pty. Ltd. (P.M.), Dee Why, New South Wales, 2086 Australia; Oxford Brookes University (A.T., N.G.), Oxford, OX3 0BP United Kingdom; and Department of Obstetrics and Gynecology, Monash University (P.M.), Clayton, Victoria, 3168 Australia

Address all correspondence to: David Robertson Ph.D., Prince Henry’s Institute of Medical Research, P.O. Box 5152, Clayton, Victoria 3168, Australia. E-mail: david.robertson{at}med.monash.edu.au

Abstract

The aim of this study was to characterize the molecular wt forms of inhibins A and B and its free -subunit present in serum from women with ovarian cancer as a basis for developing improved monoclonal antibody-based inhibin assays for monitoring ovarian cancer. Three new inhibin -subunit (C) ELISAs were developed using monoclonal antibodies directed to three nonoverlapping peptide regions of the C region of the inhibin -subunit. To characterize serum inhibin molecular wt forms present in women with ovarian cancer, existing inhibin immunoassays (inhibin A, inhibin B, and pro-C) and the new C ELISAs were applied to sera from women with granulosa cell tumors and mucinous carcinomas previously fractionated using a combined immunoaffinity chromatography, preparative SDS-PAGE, and electroelution procedure. The distribution and molecular size of dimeric inhibins and -subunit detected were consistent with known mol wt forms of inhibins A and B and inhibin -subunit and their precursor forms present in serum and follicular fluid from healthy women. The C ELISAs recognized all known forms of inhibin and the free inhibin -subunit, although differences between C ELISAs were observed in their ability to detect high mol wt forms. To assess which of the C ELISAs was preferred in application to ovarian cancer, the C ELISAs were applied to serum from a range of normal postmenopausal women (n = 61) and postmenopausal women (n = 152) with ovarian (serous, mucinous, endometrioid, clear cell carcinomas, and granulosa cell tumors) and nonovarian (breast and colon) cancers. Despite differences in their ability to detect high mol wt forms of inhibin, the C ELISAs showed similar sensitivity (i.e. proportion of cancer patients correctly detected) and specificity (proportion of controls correctly detected) indexes in the detection of mucinous carcinomas (84% and 95%) and granulosa cell tumors (100% and 95%) compared with earlier inhibin RIA or polyclonal antibody-based immunofluorometric assays. A combination of the C ELISAs with the CA125 assay, an ovarian tumor marker that has a high sensitivity and specificity for other ovarian cancers (serous, clear cell, and endometrioid), resulted in an increase in sensitivity/specificity indexes (95% and 95%) for the all ovarian cancer group. These new monoclonal antibody-based inhibin C ELISAs now provide practical and sensitive assays suitable for evaluation as diagnostic tests for monitoring ovarian cancers.

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