Human mammary gland and breast carcinoma contain immunoreactive inhibin/activin subunits: evidence for a secretion into cystic fluid

Objective: Inhibins and activins are members of the transforming growth factor beta superfamily and are known to modulate the growth and differentiation of several cell types. The present study investigated the localization of inhibin and activin subunits in human normal and pathological breast tissues. Design: A cross-sectional study comparing the expression of inhibin/activin subunits alpha, beta A and beta B in surgical specimens from women undergoing reductive mammoplasty (classified, according to the phase of the menstrual cycle, as follicular, luteal, or postmenopausal), and patients submitted to lumpectomy for fibrocystic disease, benign (intraductal papilloma, adenomyoepithelioma, and hamartoma) or malignant breast neoplams (intraductal, intralobular, and invasive carcinoma). Methods: Immunohistochemistry was used to localize inhibin alpha and activin beta A and beta B subunits in the cytoplasm of epithelial cells of mammary glands. Dimeric activin A, inhibin A and inhibin B were measured by specific two-site enzyme immunoassay in the cystic fluid collected from patients with fibrocystic disease. Results: An intense staining for the alpha inhibin subunit and a mild staining for beta A and beta B subunits were present in samples obtained from normal breast tissue regardless of menstrual cycle phase, and in fibrocystic disease and benign neoplasms. Carcinoma cells stained weakly to moderately for alpha subunit and were negative for beta A and beta B subunits. Fibrocystic disease was associated with absence of beta A subunit expression in normal epithelial cells and intense staining for all subunits in the apocrine cells, Immunoreactive inhibin A, inhibin B, and activin A were also present in cystic fluid, suggesting a local secretion of these proteins. Conclusion: These data suggest a local expression and secretion of inhibin and activin in human normal, fibrocystic disease and neoplastic breast tissues, The low expression of these proteins may facilitate abnormal cell proliferation in breast carcinoma.