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 globulin (SHBG). The purpose of this study was to investigate localization and distribution of SHBG in normal and neoplastic breast tissue. We examined 31 normal, 21 non-invasive, 52 invasive breast cancer tissues and 33 cases of recurrences and metastases of breast cancer immunohistochemically 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 oestrogen receptor (ER) content was evaluated by the ER-ICA method. Positive staining for SHBG was found exclusively in epithelial cell cytoplasm. Benign tissue was focally SHBG-positive and showed more stained cells in proliferating epithelium. Staining of neoplastic tissue was more heterogeneous. Half of the non-invasive carcinomas were SHBG-positive; particularly the highly differentiated. Independent of subtype and differentiation, invasive tumours were SHBG-negative in 32.5% of cases, while 19.3% were SHBG-positive in most cells. In 13 cases of invasive carcinomas, associated intraductal parts showed more staining for SHBG than the invasive tissue. Recurrences and metastases of breast cancer were SHBG-negative in 45.5% of cases, while only 3% were positive in most cells. SHBG-staining was unrelated to ER content. These results suggest that the demonstration of cytoplasmic SHBG represents a physiological feature of breast epithelium and its presence is compatible with a mechanism for cellular uptake of SHBG-bound sex hormones preceding their interaction with nuclear receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Meyer
S
S
Kinderklinik, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
Brumm
C
C
Stegner
H E
HE
Sinnecker
G H
GH
D014408:Biomarkers, Tumor; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007425:Intracellular Membranes / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D010144:Paget's Disease, Mammary / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D012016:Reference Values; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism* / Q000502:physiology; D013194:Staining and Labeling; D014018:Tissue Distribution
D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D012738:Sex Hormone-Binding Globulin