How is Allred score found in an IHC breast tissue image?

Question

In breast cancer immunohistochemistry (IHC), usually breast tissues are stained with ER/PR (Estrogen/Progesterone) stains so that ER/PR receptors (if present) show up. Allred score is a way of finding how well the receptors show up and if hormonal therapy can be applied or not. I have gone thru the technique from this video. Since, I am finding almost no resources on the Allred score (not even an image dataset related to it), I can't visualize how the technique works.

So, my question is can anyone explain the concept of proportion and intensity (the two components of Allred score) with an image stained for above receptors. Proportion means area of receptors showing up. Can we identify each receptor like we identify a nuclei if the tissue is stained with Ki-67? Then for intensity which is defined as "how well receptors show up". What does it mean quantitatively in an image?

Answer 1

The Allred score is based on an assessment of the percentage/proportion of tumor cells in a histopathologic specimen that stain positively and the intensity of the staining.

In 2010, the American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer described how to estimate the percentage/proportion of tumor cells staining positively and how to assess the intensity of staining:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073033/

“The percentage/proportion of tumor cells staining positively should be recorded and reported; all tumor containing areas of the tissue section on the slide should be evaluated to arrive at this percentage. The percentage can be arrived at either by estimation or by quantification, either manually by counting cells or by image analysis.” [bolded for emphasis]

“The intensity of staining should be recorded and reported as weak, moderate, or strong; this measurement should represent an estimate of the average staining of the intensity of the positively stained tumor cells on the entire tissue section relative to the intensity of positive controls run with the same batch.” [bolded for emphasis]

So, either using a microscope to look at a slide of a stained specimen or an image of a slide, count all tumor cells and then count positively stained tumor cells. Divide the positively stained tumor cells by the total tumor cells to get the percentage/proportion positively stained. Estimate intensity of staining.

The Allred score is calculated as the sum of the percentage/proportion of tumor cells staining positively and the intensity of staining using the table given here:

https://medicalcriteria.com/web/allred/

Note that the Allred score takes values of 0 or 2-8. There is no Allred score 1 because tumors that have 0 cells that stain (score on first component 0) must have an intensity value of 0 and tumors that have more than 0 and <1% of cells that stain (score on first component 1) must have an intensity of staining with a minimum value of 1.

A 2020 update of the 2010 guideline from the American Society of Clinical Oncology/College of American Pathologists has been published. It does not mention the estimation of the percentage/proportion of tumor cells staining positively or assessment of intensity of staining or describe any changes to the 2010 guidance on this topic.

https://pubmed.ncbi.nlm.nih.gov/31928354/