Why Should PR Be Tested in Breast Cancer？

Progesterone Receptor (PR) should be assessed routinely in breast cancer (BC) for the following reasons: (1) PR status not only carries prognostic significance but also provides information about the ER pathway and the level of likely clinical response to endocrine therapy; (2) PR status can be used for the molecular classification of BC into luminal A and B subtypes; (3) PR testing provides prognostic significance equivalent to Ki67 expression in BC and is included as one of the component genes in many multigene prognostic signatures that are increasingly used in the evaluation of BC; (4) PR staining can serve as a quality assurance measure for ER staining, particularly to minimize ER false-negative cases; and (5) PR testing follows the same procedures as ER, and its testing is inexpensive compared with molecular assays.

The Importance of Quality Control in Breast Cancer PR IHC Testing

PR exhibits nuclear staining. However, a range of factors—including fixation, antigen retrieval, antibody clones, reaction time, temperature, and substrate concentration—can influence PR staining intensity. Ongoing quality control and equipment maintenance are required: Initial and ongoing laboratory personnel training and competency assessment should be performed; regular, ongoing assay reassessment should be performed at least semiannually; revalidation is needed whenever there is a significant change to the test system; standard operating procedures (SOPs) should be used that include the routine use of external control materials with each batch of testing and the routine evaluation of internal normal epithelial elements as internal control, and appropriate external control on each tested slide. Cell-line controls are one of the options for external controls, which can nake sure the analytic variables include reagent degradation, instrument error, or improper antigen retrieval are operating within established parameters.

References

[1]. Rakha EA, Chmielik E, Schmitt FC, et al. Assessment of Predictive Biomarkers in Breast Cancer: Challenges and Updates[J]. Pathobiology. 2022;89(5):263-277.

[2]. Vani K, Sompuram SR, Schaedle AK, et al. The Importance of Epitope Density in Selecting a Sensitive Positive IHC Control[J]. J Histochem Cytochem. 2017 Aug;65(8):463-477.

[3]. Allison KH, Hammond MEH, Dowsett M, et al. Estrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Guideline Update[J]. J Clin Oncol. 2020 Apr 20;38(12):1346-1366.