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 fac tor beta superfamily and are known to modulate the growth and differentiati on of several cell types. The present study investigated the localization o f inhibin and activin subunits in human normal and pathological breast tiss ues. Design: A cross-sectional study comparing the expression of inhibin/activin subunits alpha, beta A and beta B in surgical specimens from women undergo ing reductive mammoplasty (classified, according to the phase of the menstr ual cycle, as follicular, luteal, or postmenopausal), and patients submitte d to lumpectomy for fibrocystic disease, benign (intraductal papilloma, ade nomyoepithelioma, and hamartoma) or malignant breast neoplams (intraductal, intralobular, and invasive carcinoma). Methods: Immunohistochemistry was used to localize inhibin alpha and activi n beta A and beta B subunits in the cytoplasm of epithelial cells of mammar y glands. Dimeric activin A, inhibin A and inhibin B were measured by speci fic 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 stain ing for beta A and beta B subunits were present in samples obtained from no rmal 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. Fibrocy stic disease was associated with absence of beta A subunit expression in no rmal epithelial cells and intense staining for all subunits in the apocrine cells, Immunoreactive inhibin A, inhibin B, and activin A were also presen t 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 tiss ues, The low expression of these proteins may facilitate abnormal cell prol iferation in breast carcinoma.