Steroid Hormone Receptor Immunohistochemistry in Breast Cancer: Past, Present, and Future

Abstract

This article reviews the development of steroid hormone receptor detection using the biochemical approach and the disadvantages inherent in these systems. The early history of methods for the in situ detection of receptors is related, culminating in the development of histologic immunoassays using monoclonal antibodies. Correlation of the latter with disease-free and overall survival and with clinical endocrine response are presented together with preliminary findings utilizing a new generation of antireceptor antibodies. Current problems with test scoring and interpretation are detailed with a section devoted to image analysis for assay quantification. Emphasis is placed on the fact that because so many different antibodies and tissue substrates have been employed in the past, these histologic receptor immunoassays cannot yet be considered to be fully validated. It is stressed that different laboratories must employ the same antibodies, substrates, detection systems and methods of scoring, and then correlate findings with measurable clinical end points. Only then can the assays be included in the brief list of approved breast cancer prognostic and predictive markers to eventually replace the routine biochemical methods of steroid receptor detection.

Correlation of mRNA for oestrogen receptor beta splice variants ERβ1, ERβ2/ERβcx and ERβ5 with outcome in endocrine-treated breast cancer

“…Oestrogen receptor alpha (ER ), as a measure of steroid hormone receptor status, is a currently accepted prognostic marker used to predict the response of an individual breast cancer to hormone therapy (Pertschuk & Axiotis 1999). However, it is known that up to 40% of breast tumours with positive ER status do not respond to endocrine therapy (Locker 1998).…”

Wild-type oestrogen receptor beta (ERβ1) mRNA and protein expression in Tamoxifen-treated post-menopausal breast cancers

“…Currently, ERa expression is regarded as a reliable prognostic marker with which to predict the response of an individual breast cancer to hormone therapy (Pertschuk and Axiotis, 1999). However, up to 40% of breast tumours with positive ERa status do not respond to endocrine manipulation (Locker, 1998).…”

Untitled

“…The evaluation of breast carcinomas for the presence of ER and PR is now routine practice and provides prognostic and other information useful for patient management (14,15). Early methods of assessing ER and PR included the quantitative biochemical dextran-coated charcoal assay and enzyme immunoassay, both of which require fresh tissue (15).…”

“…Immunohistochemistry also provided an advantage over the cytosol-based methods by allowing the identification of receptors in benign versus malignant epithelium and the assessment of heterogeneity of receptor expression in breast cancer (15). Immunohistochemistry also provided an advantage over the cytosol-based methods by allowing the identification of receptors in benign versus malignant epithelium and the assessment of heterogeneity of receptor expression in breast cancer (15).…”