Intracellular sex hormone-binding globulin (SHBG) in normal and neoplastic breast tissue — an additional marker for hormone dependency?

S. Meyer; C. Brumm; H.-E. Stegner; G. H. G. Sinnecker

doi:10.1055/s-0029-1211300

Experimental and Clinical Endocrinology & Diabetes, Inhaltsverzeichnis

Exp Clin Endocrinol Diabetes 1994; 102(4): 334-340
DOI: 10.1055/s-0029-1211300

Original

Intracellular sex hormone-binding globulin (SHBG) in normal and neoplastic breast tissue — an additional marker for hormone dependency?

S. Meyer^* , C. Brumm¹ , H.-E. Stegner¹ , G. H. G. Sinnecker^**

Kinderklinik, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany
¹Frauenklinik, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany

* This work will be part of thesis by S. M. ** To whom all correspondence should be addressed: PD Dr. Gernot H. G. Sinnecker, Klinik für Pädiatrie, Medizinische Universität zu Lübeck, Kahlhorststraße 31 — 35, Lübeck

Abstract

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Summary

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 semiquanti-tatively 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. In proliferating benign tissue and the predominantly SHBG-positive neoplastic tissues this mechanism seems to be more active compared with normal epithelium. In SHBG-negative tumours this function could be disrupted. This may represent a mechanism for modulation of oestrogen responsiveness in breast tumours.

Key words

Breast cancer - Sex Hormone-Binding Globulin (SHBG) - Oestrogen Receptor (ER)

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