ER APP, Breast Cancer

Certified under IVDR

In immunohistochemistry (IHC), estrogen receptor (ER) is used to determine prognosis and as a predictive marker for anti-estrogen in breast cancer. The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) recommends that the ER status of patients is determined on all invasive breast cancers and breast cancer recurrences [1]. It is, additionally, recommended that the ER status of the tumor is considered positive if there are at least 1 % positive tumor nuclei in a tissue sample.

This protocol can be used to determine ER positivity and negativity in a tumor, and provides the number of positive nuclei as well as the total number of nuclei. In addition, the ratio of positive nuclei and the area ratio of positive nuclei are given. Calibration of the protocol allows it to be used on images with different staining intensities. All tumor regions are identified within a region of interest (ROI), which can be outlined manually.

In EU/UK: CE IVD – for use in diagnostic procedures

Figure 1

One field of view of the original image at 20X (scaled down to fit this space). ROIs have been outlined manually (green hatched line).

Figure 2

Using un-biased counting frames in the detection of nuclei ensures that each object is counted only once.

Figure 3

Detection of all nuclei within the ROIs. Positive nuclei are marked with a red (strong), orange (medium) and yellow (weak) label and negative nuclei are marked with a blue label.

Details

Quantitative Output variables

The primary outputs of the device are:

Positive Percentage,
which is a value between 0 and 100 and is calculated as

Positive Percentage = (Number of ER positive tumor nuclei)/(Total number of tumor nuclei) × 100

Allred Score,
which is a value between 0 and 8 and is calculated as

Allred Score = Proportion Score + Intensity Score

where Proportion Score is a value between 0 and 5 which reflects the positive percentage, and Intensity Score is a value between 0 and 3 which reflects the intensity of the ER positive nuclei.

The secondary outputs of the device are:

Neg Nuclei (#), which is the number of tumor nuclei negative for ER
Pos Nuclei (#), which is the number of tumor nuclei positive for ER
Total Nuclei (#), which is the total number of tumor nuclei
Allred Proportion Score
Allred Intensity Score

Workflow

The APP functions as a standalone (semi-automatic workflow) and in an automatic workflow with the accessory APPs:

#10165 PCK VDS, Tumor Detection for detection of region(s) of interest
#20101 Invasive Tumor Detection (PDS) for detection of region(s) of interest

Staining Protocol

Staining protocols have been developed by the NordiQC and are available from their website: ER-runB17

References

1. Allison KH, Hammond MEH, Dowsett M, McKernin SE, Carey LA, Fitzgibbons PL, Hayes DF, Lakhani SR, Chavez-MacGregor M, Perlmutter J, Perou CM, Regan MM, Rimm DL, Symmans WF, Torlakovic EE, Varella L, Viale G, Weisberg TF, McShane LM, Wolff AC. Estrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Guideline Update. J Clin Oncol. 2020 Apr 20;38(12):1346-1366.