Comparative analysis of immunohistochemical and molecular genetic typing of breast cancer based on rAM100 panel
Abstract
Aim
: To assess the degree of concordance between the immunohistochemical (IHC) phenotype of breast cancer and the results of multigene mRNA expression analysis using the RAM100 panel with NanoString nCounter technology and to discuss the implications of discordance for IHC reference assessment.
Methods
: The study included 84 cases of invasive breast cancer; all underwent IHC analysis using a standard panel (estrogen receptors (ER), progesterone receptors (PR), HER2 and the proliferative activity marker Ki-67) and molecular genetic analysis of 28 key RAM100 genes using NanoString nCounter.
Results
: Discordance between IHC-defined subtype and RAM100 subtype was detected in 34.5 % (29 / 84) of cases; in 21 % (18 / 84) the discrepancies concerned subtypes for which fundamentally different systemic therapy regimens are recommended. BRCA1 mutation was detected in four cases, with two cases showing discordance for both ER and HER2 status. In paired samples (primary tumor / metastasis), phenotype change was recorded in one observation at a 3-year interval.
Conclusion
: IHC subtyping of breast cancer cannot be considered equivalent to molecular subtyping. The phenotype change phenomenon requires verification at the mRNA and genome level. Determination of nCounter count thresholds for each biological group is a separate task requiring larger series with mandatory IHC slide review.