|Hormone receptor score|
Estrogen and progesterone receptors cause effects in the cell nuclei.
The immunohistochemical detection of these two receptor groups is
possible in normal breast tissue, displaying heterogeneity not just in
correlation to the menstruation cycle. The induction of progesterone
receptors is one of the effects of estrogen receptors. Malignant
tumours of the breast – in most cases carcinoma of the breast – show
different patterns of hormone receptor expression, which are not only
of great therapeutical significance but are also important regarding
significantly longer relapse-free intervals.
|Biochemical detection of hormone receptors|
Originally, hormone receptor detection in carcinomas of the breast was
based on the biochemical receptor detection [radio immuno assay (RIA),
radio ligand method] in the tumour homogenate [dextran-coated charcoal
assay (DCCD)]. In this technique, the capacity of free receptors
for 3H-labeled estradiol is determined in the cytosole. Occupied
receptors escape this detection, so it is not possible to deduct the
absolute receptor content. The biochemical unit was 1 femtomol (1fmol)
of bound 3H estradiol per mg tissue protein [score: up to 10 fmol / mg
definitely negative, 11 – 20 fmol / mg borderline, 21 – 100 fmol / mg
positiv, > 100 fmol / mg highly positive].
However, this method had severe drawbacks:
|Immuno histochemical hormone receptor detection|
|During the 1980’s, antibodies against estrogen receptors were developed. At that time, using frozen sections, it was found that hormone receptors were located in the nuclei and displayed an heterogeneous staining intensity. The development of new antibody generations and new immuno histochemical demasking techniques made it possible to detect estrogen and progesterone receptors in formalin-fixed and paraffine-embedded breast tissue, obtaining distinct, reproducible results. The immuno histochemical detection [ER-ICA, PgR-ICA (estrogen - / progesterone receptor immuno cytochemical assay)] permits the direct, visual demonstration of the nuclear receptor protein including free and occupied receptors, using monoclonal antibodies.|
Cell nuclei with positive reactions show, in correlation to the
employed chromo gen (in this case DAB) a brown to dark brown staining
pattern, which may be characterized by a varying degree of staining
intensity, such as homogeneous or heterogeneous expression.
Receptor-negative carcinoma show only indistinctly visible, pale cell
nuclei. The cytoplasm of the tumour cells and that of cells surrounding
the stroma reveals no staining reaction. By simultaneous labeling it
was possible to show that tumour cells co-express ER and PR or,
alternatively, express only ER or PgR. The receptor distribution
pattern suggests a tumour individualisation. This direct detection
method captures the receptor proteins in the tissue unit, regardless of
the quantity of the available material.
Two scoring systems are in use, providing a uniform wording of the report:
|Immuno reactive score hormone receptors according to Remmele and Stegner („Pathologe“, 1987)|
Percentage of positive cells:
Immuno reactive score (IRS): SI x PP
|Total score (TS) according to DC Allred (MD 1998)|
Based on this, intensity score (IS) and proportion of positive cell
nuclei (proportion score, PS) are proposed as factors, their scores
transfered into the product giving the total score (TS) (with possible
values from 0 to 8).
Total Score (TS) = IS + PS
copyright © 2006, all rights reserved
dr. med. michael respondek, facharzt für pathologie
kapitelplatz 9, 49377 vechta