S Luisi, P Florio, FM Reis and F Petraglia
C Di Loreto, FM Reis, P Cataldi, C Zuiani, S Luisi, CA Beltrami and F Petraglia
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, betaA and betaB 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 betaA and betaB 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 betaA and betaB 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 betaA and betaB subunits. Fibrocystic disease was associated with absence of betaA 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.
L Cobellis, P Cataldi, FM Reis, G De Palo, F Raspagliesi, S Pilotti, F Arcuri and F Petraglia
OBJECTIVE: Inhibin and activin are proteins produced by ovarian granulosa cells and testicular Sertoli cells and are members of the transforming growth factor-beta superfamily. Since increased circulating levels of immunoreactive inhibin were detected in women with malignant ovarian tumors, they were proposed as tumor markers for ovarian carcinoma. Immunohistochemical studies later confirmed the presence of inhibin and activin subunits in granulosa cell tumors and epithelial ovarian cancer, as well as in Sertoli and Leydig cell testicular cancer. However, there is discrepant information on the detection of inhibin and activin in malignant germ cell tumors (MGCT). The aim of the present study was to evaluate the immunohistochemical expression of the inhibin/activin alpha, betaA and betaB subunits in ovarian and testicular MGCT specimens using polyclonal antisera. METHODS: The ovarian tissue samples were composed of 19 MGCT, including dysgerminoma (n=18) and yolk sac tumor (n=1). The testis specimens included classic seminomas (n=20), embryonal carcinomas (n=7), choriocarcinomas (n=2), and yolk sac tumor (n=1). RESULTS: Ovarian and testicular malignant germ cell tumors expressed positive staining for inhibin/activin alpha, betaA and betaB subunits, with some variations between and within individual tumors: while ovarian dysgerminomas were diffusely positive for alpha, betaA and betaB, testicular tumors expressed alpha and betaB subunits, whereas betaA staining was weak. CONCLUSIONS: The present results show positive staining for inhibin/activin subunits in ovarian and testicular MGCT, suggesting a possible role in tumorigenesis with the resultant clinical implication.