Abstract
Background: Testing for HER2 amplification and/or overexpression is currently routine practice to guide Herceptin therapy in invasive breast cancer. At present, HER2 status is most commonly assessed by immunohistochemistry (IHC). Standardization of HER2 IHC assays is of utmost clinical and economical importance. At present, HER2 IHC is most commonly performed with the HercepTest which contains a polyclonal antibody and applies a manual staining procedure. Analytical variability in HER2 IHC testing could be diminished by a fully automatic staining system with a monoclonal antibody.Materials and Methods: 219 invasive breast cancers were fully automatically stained with the monoclonal antibody-based Oracle HER2 Bond IHC kit and manually with the HercepTest. All cases were tested for amplification with chromogenic in situ hybridization (CISH).Results: HercepTest yielded an overall sharper membrane staining, with less cytoplasmic and stromal background than Oracle in 17% of cases. Overall concordance between both IHC techniques was 89% (195/219) with a kappa value of 0.776 (95% CI 0.698–0.854), indicating a substantial agreement. Most (22/24) discrepancies between HercepTest and Oracle showed a weaker staining for Oracle. Thirteen of the 24 discrepant cases were high-level HER2 amplified by CISH, and in 12 of these HercepTest IHC better reflected gene amplification status. All the 13 HER2 amplified discrepant cases were at least 2+ by HercepTest, while 10/13 of these were at least 2+ for Oracle. Considering CISH as gold standard, sensitivity of HercepTest and Oracle was 91% and 83%, and specificity was 94% and 98%, respectively. Positive and negative predictive values for HercepTest and Oracle were 90% and 95% for HercepTest and 96% and 91% for Oracle, respectively.Conclusion: Fully-automated HER2 staining with the monoclonal antibody in the Oracle kit shows a high level of agreement with manual staining by the polyclonal antibody in the HercepTest. Although Oracle shows in general some more cytoplasmic staining and may be slightly less sensitive in picking up HER2 amplified cases, it shows a higher specificity and may be considered as an alternative method to evaluate the HER2 expression in breast cancer with potentially less analytical variability.
Highlights
HER-2/neu is a proto-oncogene located on chromosome 17q21 encoding a 185 kD transmembrane tyrosine kinase receptor protein that is involved in signal transduction [1,15]
Thirteen of the 24 discrepant cases were high-level HER2 amplified by chromogenic in situ hybridization (CISH), and in 12 of these HercepTest IHC better reflected gene amplification status
Fully-automated HER2 staining with the monoclonal antibody in the Oracle kit shows a high level of agreement with manual staining by the polyclonal antibody in the HercepTest
Summary
HER-2/neu is a proto-oncogene located on chromosome 17q21 encoding a 185 kD transmembrane tyrosine kinase receptor protein that is involved in signal transduction [1,15]. HER2 belongs to the human epidermal growth factor receptor (EGFR) family and is amplified in about 15–25% of breast carcinomas causing an increased expression of its protein [13, 17,20]. Patients having this overexpression respond well to treatment with trastuzumab (Herceptin®), a recombinant humanized monoclonal anti-HER2 antibody [5,21]. Amplification and overexpression of HER2 has been shown to correlate with poor prognosis [7] and with resistance to conventional adjuvant chemotherapy and tamoxifen [3,4,18,19,24] For these reasons, testing for HER2 amplification and/or overexpression is currently considered routine practice in clinical pathology laboratories. Analytical variability in HER2 IHC testing could be diminished by a fully automatic staining system with a monoclonal antibody
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
