Classifications Praxis für Pathologie Vechta
Hormone receptor score
Basics
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: 
  • tumour sampling error, caused by the need to use a minimum quantity of 0,5 g of fresh material
  • contamination error, caused by attached normal breast tissue
  • analytical errors
  • logistical / procedural error, caused by the need keep the cancer tissue cool immediately after the excision.
The  advantage of this biochemical method was that a quantitative result was obtained.
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)
Staining intensity:
staining intensity 0 = negative   staining intensity 1 = weak
Fig. 1
(SI): 0 = negative
  Fig. 2
(SI): 1= weak
staining intensity 2 = moderate   staining intensity 3 = strongly positive
Fig. 3
(SI): 2 = moderate
  Fig. 4
(SI): 3 = strongly positive
Based on this, staining intensity (SI) and the percentage of positive cell nuclei (PP) are proposed as factors, their scores transfered into the product giving the immuno reactive score (IRS) (with possible values from 0 to 12).
Percentage of positive cells:
PP score 0 = negative
  PP score 1 =  < 10 per cent positive cells)

PP score 2 = 10 – 50 per cent positive cells
Fig. 1 | PP = 0 (negative)
  Fig. 2 | PP =  1 (> 10 per cent positive cells)   Fig. 3 | PP = 2 (10 – 50 per cent positive cells)
PP score 3 = 51 – 80 per cent positive cells)
  PP score 4 = > 80 per cent positive cells
   
Fig. 4 | PP = 3 (51 – 80 per cent positive cells)
  Fig. 5 | PP = 4 (> 80 per cent positive cells)  


Immuno reactive score (IRS): SI x PP
immuno reactive score of hormone receptors
Interpretation:
  • 0 – 2: IRS negative
  • ≥ 3: IRS positive
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
Total score (TS) according to DC Allred (MD 1998)
Interpretation:
  • 0 – 2: TS negative
  • ≥3: TS positive

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dr. med. michael respondek, facharzt für pathologie
kapitelplatz 9, 49377 vechta