INTRACELLULAR SEX HORMONE-BINDING GLOBULIN (SHBG) IN NORMAL AND NEOPLASTIC BREAST-TISSUE - AN ADDITIONAL MARKER FOR HORMONE DEPENDENCY

Recent studies indicate that in addition to free diffusion, uptake of sex hormones into target cells is mediated by sex hormone-binding glob ulin (SHBG). The purpose of this study was to investigate localization and distribution of SHBG in normal and neoplastic breast tissue. We e xamined 31 normal, 21 non-invasive, 52 invasive breast cancer tissues and 33 cases of recurrences and metastases of breast cancer immunohist ochemically for SHBG by the ABC-peroxidase method, using a polyclonal, monospecific antiserum derived from rabbit. The proportion of stained cells was evaluated semiquantitatively. In 81 malignant cases the oes trogen receptor (ER) content was evaluated by the ER-I Positive staini ng for SHBG was found exclusively in epithelial cell cytoplasm. Benign tissue was focally SHBG-positive and showed more stained cells in pro liferating epithelium. Staining of neoplastic tissue was more heteroge neous. Half of the non-invasive carcinomas were SHBG-positive; particu larly the highly differentiated. Independent of subtype and differenti ation, invasive tumours were SHBG-negative in 32.5% of cases, while 19 .3% were SHBG-positive in most cells. In 13 cases of invasive carcinom as, associated intraductal parts showed more staining for SHBG than th e invasive tissue. Recurrences and metastases of breast cancer were SH BG-negative in 45.5% of cases, while only 3% were positive in most cel ls. SHBG-staining was unrelated to ER content. These results suggest t hat the demonstration of cytoplasmic SHBG represents a physiological f eature of breast epithelium and its presence is compatible with a mech anism for cellular uptake of SHBG-bound sex hormones preceding their i nteraction with nuclear receptors. In proliferating benign tissue and the predominantly SHBG-positive neoplastic tissues this mechanism seem s to be more active compared with normal epithelium. In SHBG-negative tumours this function could be disrupted. This may represent a mechani sm for modulation of oestrogen responsiveness in breast tumours.