Abstract
BACKGROUND AND AIMS: Hormone receptors are expressed in 70% of breast cancers and are the major biomarkers for tailoring treatment in early-stage breast cancer. In clinical routine, immunohistochemistry (IHC) is used to assess estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67 protein expression. However, IHC procedure is challenged with pre-analytical and analytical variability. Pathologist interpretation of IHC results can vary, and discordant results between local and reference laboratories have been reported. Using mRNA-based tests may be a more robust, reliable, and standardized method to assess these important breast cancer biomarkers. This study aimed to assess the concordance between real-time PCR and IHC results. METHODS: In this study, we analyzed 178 early-stage hormone receptor-positive breast tumors. IHC for ER, PR, HER2, and Ki67 had been previously performed for the study samples at local laboratories. For samples with HER2 IHC score 2+, Fluorescence In Situ Hybridization was performed. ESR1 (encoding ER), PGR (encoding PR), ERBB2 (encoding HER2), and MKI67 (encoding Ki67) mRNA expression were determined using TaqMan gene expression assays. RESULTS: The overall concordance between mRNA expression results and their corresponding IHC markers was 95.9% for ESR1/ER, 79.3% for PGR/PR, and 100% for ERBB2/HER2. There was a moderate correlation between MKi67 mRNA values and Ki67 IHC. ESR1 expression was significantly lower in tumors of younger patients (p < 0.001). No statistically significant correlation between age at cancer diagnosis and ER IHC was identified. Higher ESR1 and MKI67 mRNA expression was associated with worse pathological characteristics. CONCLUSIONS: PCR-based classification of breast tumors in a central laboratory may be used to confirm the available IHC results performed at local laboratories and add valuable information for patient management. mRNA-based biomarkers may be promising for more standardized breast cancer management.