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. 2024 Sep;85(3):437-450.
doi: 10.1111/his.15193. Epub 2024 Apr 23.

Concordance between ER, PR, Ki67, and HER2-low expression in breast cancer by MammaTyper RT-qPCR and immunohistochemistry: implications for the practising pathologist

Nahla M Badr  1   2 , Mohamed Zaakouk  1   3 , Qi Zhang  4 , Daniel Kearns  5 , Anthony Kong  1   6 , Abeer M Shaaban  1   5
Affiliations

Concordance between ER, PR, Ki67, and HER2-low expression in breast cancer by MammaTyper RT-qPCR and immunohistochemistry: implications for the practising pathologist

Nahla M Badr et al. Histopathology. 2024 Sep.

Abstract

Background: There are limited data on the role of multigene tests and their correlation with immunohistochemistry (IHC), especially on core biopsy. MammaTyper is a quantitative conformite Europeeanne (CE) marked, National Institute for Health and Care excellence (NICE) approved, in in vitro diagnostic quantitative real-time polymerase chain reaction (RT-qPCR) test for assessment of mRNA expression of four biomarkers (ESR1, PGR, ERBB2, MKI67).

Methods: We evaluated the concordance of MammaTyper with oestrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67 by IHC on 133 core needle biopsies of breast cancer. HER2 was positive if IHC 3+ or 2+ and fluorescence in situ hybridization (FISH)-amplified. Global and hotspot Ki67 expression was analysed using a cutoff of ≥20% assessed manually and by digital image analysis. Agreements were expressed as overall percent agreement (OPA), positive percent agreement (PPA), negative percent agreement (NPA), and Cohen's kappa.

Results: RT-qPCR results of ESR1 were highly concordant with IHC with OPA of 94.7% using 1% cutoff and 91.7% when the low ER-positive category was included. The PPA and NPA between RT-qPCR and IHC for PR was 91.5% and 88.0%, respectively, when using the 1% cutoff. For ERBB2/HER2, the OPA was 95% and the PPA was 84.6%. 40 of 72 HER2 IHC score 0 tumours were classified as ERBB2 low. Best concordance between MKI67 by MammaTyper and Ki67 IHC was achieved using hotspot digital image analysis (OPA: 87.2%, PPA: 90.6%, NPA: 80%).

Conclusion: RT-qPCR-based assessment of the mRNA expression of ESR1, PGR, ERBB2, and MKI67 showed high concordance with IHC, suggesting that the MammaTyper test on core needle biopsies represents a reliable, efficient, and reproducible alternative for breast cancer classification and refining HER2 low categorisation.

Keywords: HER2; HER2‐low; Ki67; breast cancer; oestrogen receptor; progesterone receptor.

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References

    1. Nielsen TO, Leung SCY, Rimm DL et al. Assessment of Ki67 in breast cancer: updated recommendations from the international Ki67 in breast cancer working group. J. Natl. Cancer Inst. 2021; 113; 808–819.
    1. Hammond ME, Hayes DF, Dowsett M et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J. Clin. Oncol. 2010; 28; 2784–2795.
    1. Rakha EA, Tan PH, Quinn C et al. UK recommendations for HER2 assessment in breast cancer: an update. J. Clin. Pathol. 2023; 76; 217–227.
    1. Wolff AC, Somerfield MR, Dowsett M et al. Human epidermal growth factor receptor 2 testing in breast cancer: Asco‐College of American Pathologists guideline update. Clin. Oncol. 2023; 41; 3867–3872.
    1. McLemore LE, Albarracin CT, Gruschkus SK et al. HER2 testing in breast cancers: comparison of assays and interpretation using ASCO/CAP 2013 and 2018 guidelines. Breast Cancer Res. Treat. 2021; 187; 95–104.

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