Evaluation of ERBB2 mRNA Expression in HER2-Equivocal (2+) Immunohistochemistry Cases

SIMPLE SUMMARY: HER2-equivocal cases represent around 15% of breast carcinomas, and 20–40% of them are HER2-amplified. The distinction between HER2-amplified and non-amplified cases is of great importance for patient management, and in this study, we investigated the performance of STRAT4 (a RT-qPCR platform) in the evaluation of HER2-equivocal cases. We compared this technique to the recommended methods (immunohistochemistry and in situ hybridization) for the evaluation of HER2-equivocal cases and non-equivocal HER2 cases. We found a 91.3% accuracy for the identification of HER2-positive tumors globally and 99.3% for that of non-equivocal HER2 cases, while the accuracy decreased to 80.7% for HER2-equivocal cases. Our results suggest that STRAT4 is not reliable for the evaluation of the HER2 amplification status in equivocal cases. ABSTRACT: Xpert Breast Cancer STRAT4 is a RT-qPCR platform that studies the mRNA expression of ESR1, PGR, MKI67 and ERBB2, providing a positive or negative result for each of these breast cancer biomarkers. Its concordance with immunohistochemistry (IHC) and in situ hybridization (ISH) has been previously demonstrated, but none of the previous works was focused on HER2-equivocal (2+) cases identified by IHC. Thus, we studied the concordance between IHC/ISH and STRAT4 results for 112 HER2 2+ IBC samples, using 148 HER2 0+, 1+ and 3+ (no-HER2 2+) samples for comparison. We found 91.3% accuracy for the determination of HER2 status globally, 99.3% for no-HER2 2+ samples and 80.7% for HER2 2+ samples. Regarding the other biomarkers, we obtained 96.4% accuracy for estrogen receptor, 84.1% for progesterone receptor and 58.2% for Ki67. Our results suggest that the use of ERBB2 mRNA for the evaluation of HER2 2+ cases is not a reliable reflex method to assess the ERBB2 amplification status.