Comparison of the ASCO/CAP and the Allred Scoring/Interpretation Methods in Determination of Estrogen Receptor (ER) and Progesterone Receptor (PgR) Immunoreactivity Using an Immunohistochemical (IHC) Assay.
Rosanne Welcher, Therese Phillips, Dennis Chenoweth. Dako NA, Carpinteria, CA
Background: The Dako ER/PR pharmDx™ Kit is an FDA-cleared product identifying ER and PgR expression in normal and neoplastic FFPE tissues. The kit was clinically validated by comparison of positive and negative specimens defined by the Allred scoring/interpretation method (Allred System). Subsequently, an Expert Panel representing ASCO and CAP has published guidelines for IHC testing and results reporting for ER and PgR in breast CA. As pointed out by the ASCO/CAP panel, the ER/PR pharmDx Kit is one example of an assay format that meets the analytical and clinical validation criteria against which labs can validate their assays. The ASCO/CAP guideline for interpretation defines a specimen as ER or PR positive if ≥1% of tumor cell nuclei are immunoreactive. The pathologist may also provide a composite score such as an H, Allred or Quick score. The objective of the current study was to compare the ER and PR results obtained with the ER/PRpharmDx Kit using the Allred System to the results obtained using the ≥1% cut-off for positivity recommended by ASCO/CAP.
Design: The original concordance testing of the ER/PRpharmDx Kit to clinically validated IHC protocols (Harvey ER and Mohsin PR) was conducted on IBC tissues. Results were determined using the Allred Sytem for all protocols. Concordance of at least 90% between the Harvey ER and Mohsin PR protocols and the ER/PR Kit was required. For this investigation, the raw data for these specimens was re-analyzed using the ASCO/CAP guidelines for positivity.
Results: The ER results using the Allred System for 212 tissues were 99.5% concordant with the ASCO/CAP guideline results. The PgR scores using the Allred System for 203 tissues were 98% concordant with the ASCO/CAP guideline results. Of 212 cases, one discordant ER case was positive with the Allred System and negative using the ≥1% cut-off for positivity. Of 203 cases, four discordant PgR cases were positive with the Allred System and negative using the ≥1% cut-off for positivity. These discordant cases demonstrated <1% of positively stained cells but at moderate intensity.
Conclusions: The results generated by the ER/PR pharmDx Kit and initially interpreted using the Allred System exhibit a high degree of concordance with results generated by re-analysis of the raw data using the definition of positivity as ≥1% tumor nuclei staining. The frequency of discordant results was low. These data support that use of either the ASCO/CAP interpretation guidelines or the Allred System would be effective for patient diagnosis.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 53, Tuesday Morning