Implementation of American Society of Clinical Oncology/College of American Pathologists HER2 Guideline Recommendations in a tertiary care facility increases HER2 immunohistochemistry and fluorescence in situ hybridization concordance and decreases the number of inconclusive cases.
ABSTRACT The American Society of Clinical Oncology/ College of American Pathologists (ASCO/CAP) guideline recommendations from January 2007 identified many sources of immunohistochemistry (IHC) testing variation.
In this current study, we implemented the guidelines and addressed our institution's preanalytic, analytic, and postanalytic variables relating to HER2 testing to improve clinical outcomes.
We evaluated core biopsies performed on breast lesions from 2006 through 2007. Prognostic/predictive markers obtained by IHC were correlated with HER2 fluorescence in situ hybridization (FISH). Preanalytic sources of biopsy testing variation were studied by collecting data on the number of biopsies that needed repeat testing because of inconclusive FISH results.
In the year preceding implementation of the guidelines, the HER2 IHC and FISH concordance was 98%. In an additional 10.8% of cases, the FISH results were inconclusive. When additional material became available to retest the inconclusive cases, the results were informative. Further evaluation of the inconclusive cases revealed that the core needle biopsies received, on average, 4 hours of formalin fixation. After implementation of a minimum 6 hours of fixation and the ASCO/CAP guideline recommendations, the HER2 IHC and FISH concordance was 98.5%. The number of FISH inconclusive cases decreased from 10.8% to 3.4% (a 64% reduction). Repeat estrogen-receptor IHC requests decreased by 40% from 38 in 2006 to 23 in 2007.
We have shown that standardized fixation and adherence to the ASCO/CAP guidelines for HER2 testing has resulted in a greater HER2 IHC and HER2 FISH correlation, decreased numbers of inconclusive FISH cases, decreased repeat estrogen-receptor requests, and financial savings to the Department of Pathology.
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ABSTRACT: Human epidermal growth factor receptor 2 (HER2) overexpression is present in approximately 15% of early invasive breast cancers, and is an important predictive and prognostic marker. The substantial benefits achieved with anti-HER2 targeted therapies in patients with HER2-positive breast cancer have emphasised the need for accurate assessment of HER2 status. Current data indicate that HER2 test accuracy improved following previous publication of guidelines and the implementation of an external quality assessment scheme with a decline in false-positive and false-negative rates. This paper provides an update of the guidelines for HER2 testing in the UK. The aim is to further improve the analytical validity and clinical utility of HER2 testing by providing guidelines of test performance parameters, and recommendations on the postanalytical interpretation of test results. HER2 status should be determined in all newly diagnosed and recurrent breast cancers. Testing involves immunohistochemistry with >10% complete strong membrane staining defining a positive status. In situ hybridisation, either fluorescent or bright field chromogenic, is used either upfront or in immunohistochemistry borderline cases to detect the presence of HER2 gene amplification. Situations where repeat HER2 testing is advised are outlined and the impact of genetic heterogeneity is discussed. Strict quality control and external quality assurance of validated assays are essential. Testing laboratories should perform ongoing competency assessment and proficiency tests and ensure the reliability and accuracy of the assay. Pathologists, oncologists and surgeons involved in test interpretation and clinical use should adhere to published guidelines and maintain accurate performance and consistent interpretation of test results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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ABSTRACT: Clinical decisions regarding the suitability of adjuvant systemic therapy for individual patients with breast cancer depends on comprehensive assessment of the underlying biology of each patient's tumor. The previous clinical-pathologic paradigm for treatment, which had been used for decades, now has been augmented by significant advances in molecular analysis of breast tumor tissue samples. Molecular testing has the potential to understand better both tumor biology and clinical behavior, which enables more appropriate therapy choices to be made. We review the rapid evolution in profiling breast cancer tissues, and discuss the current evidence for clinical use of this information and how the emerging molecular paradigm can be integrated into the clinical-pathologic context as we progress toward "precision" therapy for patients with breast cancer and other solid tumors.Biotechnic and Histochemistry 12/2014; 90(2):1-12. DOI:10.3109/10520295.2014.978893 · 1.00 Impact Factor
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ABSTRACT: It has been proven that chromosome 17 centromere (CEP17) amplification causes misleading human epidermal growth factor receptor 2 (HER2) gene fluorescence in situ hybridization (FISH) results, precluding anti-HER2-based therapy in some patients with breast carcinoma. We used the 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) scoring criteria to evaluate HER2 amplification status in 175 cases of breast carcinoma with chromosome 17 polysomy. We used immunohistochemistry (IHC) to determine the HER2 amplification status, and 2-color FISH to detect CEP17, and reviewed the results of initial evaluation using the 2007 ASCO/CAP criteria. Of the 175 cases, 17, 95, and 63 were IHC 0/1+, 2+, and 3+, respectively. Evaluation of IHC HER2 status according to the 2013 ASCO/CAP criteria identified significantly more HER2-positive cases compared to cases evaluated using the 2007 criteria (p<0.05). When the FISH results were evaluated in parallel with the 2013 criteria, we found that 22 cases were not HER2-negative despite the presence of polysomy 17, which, according to the 2013 criteria, indicates HER2-positive status. Our findings indicate that in breast carcinoma, HER2 status in the presence of polysomy 17 may vary with the scoring criteria used. In turn, performing FISH and evaluating samples using the 2013 ASCO/CAP criteria means that more patients with breast cancer may be appropriate for targeted treatment with trastuzumab, potentially improving their outcome. Copyright © 2014 The Authors. Published by Elsevier GmbH.. All rights reserved.Pathology - Research and Practice 11/2014; 211(6). DOI:10.1016/j.prp.2014.09.010 · 1.56 Impact Factor