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Characteristics
Estrogen receptor (ER) belongs to the steroid
receptor superfamily of nuclear receptors. It is a protein with
553 amino acids. The receptor molecule has three domains, i.e.
the central DNA-binding domain, the hormone-binding domain at
the C-terminal, and the transcription-activating domain at the
N-terminal. ER mediates regulatory functions of female sex
steroids, mainly 17
(E2), on growth,
differentiation and function in several target tissues, including female
and male reproductive tract, mammary gland, and skeletal and
cardiovascular systems. Immunohistochemical demonstration of
ERα in normal tissues is
illustrated in Fig. 1.
Recently, a
second estrogen receptor, termed ERβ,
was discovered. Human ERβ
shares a high structural homology with the previously known human ER, now
termed ERα,
especially in the DNA- and hormone binding domains. Both receptors bind
hormones with similar affinity and their transcriptional activation is
identical. The tissue distribution of ERβ
is similar to that of ERα
with some differences. In normal and malignant human breast tissue ERβ
is expressed in stromal cells in addition to epithelia. Only limited data
are available on the role of ERβ
in normal and neoplastic tissues.
Neoplasms
ERα is mainly
expressed in tumours of female sex steroid hormone responsive tissues such
as the mammary gland, endometrium, and ovary. Immunohistochemical
demonstration of ERα in
neoplastic tissues is illustrated in Fig. 2.
ERα
protein is expressed in 60-70% of female breast cancers (ER+/PR- 19-22%; ER+/PR+ 49-53%). Other tumours expressing
ERα are meningiomas, salivary gland tumours, some neuroendocrine
tumours, and some colorectal and hepatocellular
carcinomas.
Application
The applications of immunohistochemical demonstration of ERα
are two-fold. The main clinical use of ERα
immunohistochemistry is prediction of response to therapy in breast
carcinoma. Tumours expressing both ERα and PR react positively to antiestrogen therapy in 50-70% of cases as against below 10% of
those negative for ERα and PR. Based on these facts and a number
of meta-analyses, adjuvant antiestrogen treatment is
administered in most countries to postmenopausal women with ER+
breast cancer. In addition to predicting treatment response, the
ERα (and PR) status can be used to estimate disease-free and
overall survivals of breast carcinoma patients. In newer studies
with immunohistochemical assay, positive steroid hormone status
has predicted favourable overall, survival, independently of
hormonal treatment.
Secondly, ERα can be used as a tumour marker (see Neoplasms above), preferentially in
combination with an antibody to
Progesterone receptor , e.g., in
the classification of adenocarcinomas.
Visualization
Positive staining reaction is seen in nuclei of the cells of the
target tissue. In breast carcinoma, epithelial cells of both ductal and
lobular origin display nuclear staining.
Efficient HIER is mandatory. The mAbs clone 6F11, SP1 (rabbit
mAb) and 1D5 can all be used. However, the latter has less affinity than
the others and therefore makes heavier demands on the protocol.
Control tissue:
Normal
breast epithelial cell nuclei
are often used as an internal control.
However, uterine cervix is an attractive alternative, as the
staining reaction in epithelial and stromal cells is readily assessed. A
strong staining of the large majority of columnar and squamous
epithelial cells should be seen.
Assessments
Run 8
2003
Run
10 2004
Run 13 2005
Run B1 2006
Run B3 2007
Run B5 2008
Run B7 2009
Run B8 2009
Run B10 2010
Run B11 2011
Run B13
2012
Run B15
2013
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