Abstract
We report here the results of the analytical validation of assays that measure HER2 total protein (H2T) and HER2 homodimer (H2D) expression in Formalin Fixed Paraffin Embedded (FFPE) breast cancer tumors as well as cell line controls. The assays are based on the VeraTag technology platform and are commercially available through a central CAP-accredited clinical reference laboratory. The accuracy of H2T measurements spans a broad dynamic range (2-3 logs) as evaluated by comparison with cross-validating technologies. The measurement of H2T expression demonstrates a sensitivity that is approximately 7–10 times greater than conventional immunohistochemistry (IHC) (HercepTest). The HERmark assay is a quantitative assay that sensitively and reproducibly measures continuous H2T and H2D protein expression levels and therefore may have the potential to stratify patients more accurately with respect to response to HER2-targeted therapies than current methods which rely on semiquantitative protein measurements (IHC) or on indirect assessments of gene amplification (FISH).
Highlights
The human epidermal growth factor receptor 2 (HER2) is a transmembrane protein tyrosine kinase receptor that is important in initiating signal transduction pathways in normal and abnormal cells [1,2,3,4,5]
The HER2 total assay configuration (Figure 1(a)) consists of a VeraTag reporter conjugated to a specific antibody (Ab-1) that binds a distinct epitope of HER2, while biotin is conjugated to a second antibody (Ab-2) that recognizes a second unique HER2 epitope
A secondary streptavidin-methylene blue conjugate is bound to the biotin-antibody complex to form a photosensitizer molecule (PM)
Summary
The human epidermal growth factor receptor 2 (HER2) is a transmembrane protein tyrosine kinase receptor that is important in initiating signal transduction pathways in normal and abnormal cells [1,2,3,4,5]. HER2 is overexpressed/amplified in approximately 15%–30% of human breast tumors and is a biomarker of poor prognosis in patients demonstrating either high protein levels and/or gene amplification on chromosome 17 [4, 6, 7]. For this reason, HER2 testing is recommended for all newly diagnosed breast cancer patients for the selection of individuals that may benefit from treatment with the humanized monoclonal antibody Trastuzumab [8,9,10,11]. The ability to accurately and Pathology Research International reproducibly quantify the level of HER2 protein expression in tumors is critical to the appropriate selection of patients for Trastuzumab and other HER2 targeted therapies
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