Chromogenic In Situ Hybridization Is a Reliable Method for Detecting HER2 Gene Status in Breast Cancer A Multicenter Study Using Conventional Scoring Criteria and the New ASCO/CAP Recommendations
ABSTRACT Chromogenic in situ hybridization (CISH) has shown the potential to replace fluorescence in situ hybridization (FISH) to determine HER2 gene status. To validate the reliability of CISH, we used 226 consecutive breast carcinomas from 2 institutions and tested CISH and FISH on the same tumor set simultaneously at different test sites. Besides manufacturers' scoring criteria, the new American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines were used to interpret HER2 status. The concordance between CISH and FISH for positive and negative results was 98.5% at site A and 98.6% at site B using the manufacturers' criteria, and 99.0% at site A and 99.1% at site B using the ASCO/CAP criteria. Reproducibility of CISH results was more than 98.0% among 3 sites using the manufacturers' criteria and 100.0% between 2 sites using the ASCO/CAP criteria. Our results confirm that CISH is reliable for HER2 testing per ASCO/CAP guidelines.
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ABSTRACT: The purpose was to evaluate and compare 5 different HER2 genetic assays with different characteristics that could affect the performance to analyze the human epidermal growth factor 2 (HER2) gene copy number under low and high throughput conditions. The study included 108 tissue samples from breast cancer patients with HER2 immunohistochemistry (IHC) results scored as 0/1+, 2+, and 3+. HER2 genetic status was analysed using chromogenic in situ hybridization (CISH) and fluorescence in situ hybridization (FISH). Scoring results were documented through digital image analysis. The cancer region of interest was identified from a serial H&E stained slide following tissue cores were transferred to a tissue microarrays (TMA). When using TMA in a routine flow, all patients will be tested for HER2 status with IHC followed by CISH or FISH, thereby providing individual HER2 results. In conclusion, our results show that the differences between the HER2 genetic assays do not have an effect on the analytic performance and the CISH technology is superior to high throughput HER2 genetic testing due to scanning speed, while the IQ-FISH may still be a choice for fast low throughput HER2 genetic testing.12/2013; 2013:368731. DOI:10.1155/2013/368731
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ABSTRACT: This study specifically addressed the performance of chromogenic in situ hybridization (CISH) on HER2 testing in 66 breast carcinomas with chromosome 17 polysomy and 49 carcinomas with an equivocal HercepTest (DakoCytomation, Carpinteria, CA) score by comparing CISH with corresponding FISH results at 2 test sites and evaluating intersite agreement of CISH results. For tumors with chromosome 17 polysomy, when using the manufacturers' criteria, the concordance values between CISH and FISH at site A, site B, and intersite CISH agreement were 95.8%, 95.5%, and 93.5%, respectively; when using the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria, the values were 100.0%, 100.0%, and 100.0%, respectively. For tumors with an equivocal HercepTest score, when using the manufacturers' criteria, the concordance values between the 2 methods at site A, site B, and intersite CISH agreement were 88.2%, 95.1%, and 91.1%, respectively; when using the ASCO/CAP criteria, the values were 96.7%, 97.3%, and 97.4%, respectively. These results indicate that CISH is reliable for testing these 2 types of tumors, especially when the ASCO/CAP criteria are used.American Journal of Clinical Pathology 09/2009; 132(2):228-36. DOI:10.1309/AJCP4M2VUZCLDALN · 3.01 Impact Factor
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ABSTRACT: Trastuzumab is a monoclonal antibody directed against the human EGFR2 (HER2) protein that has been shown to improve survival in patients with HER2-positive breast cancer. Lapatinib is an oral small-molecule tyrosine kinase inhibitor directed against EGFR and HER2. Lapatinib therapy was shown to prolong the time to progression and increase the rate of response to capecitabine in patients who had received anthracycline-based and taxane-based chemotherapy, and whose tumors had progressed on trastuzumab. HER2 status, either gene copy number or the protein expression level, is the best predictive marker available for assessing response to trastuzumab and lapatinib. Whether the power of this predictive marker is the same in advanced and early-stage cancers is unknown. There is great interest in developing diagnostic tests that predict which patients are more likely to benefit from specific HER2-directed therapies. Novel therapeutics that will overcome resistance to trastuzumab and lapatinib are under intense clinical development. In the future, it will be important to characterize mechanisms of resistance in metastatic tumors to determine which novel targeted therapy will be most appropriate for individual patients.Nature Reviews Clinical Oncology 12/2009; 7(2):98-107. DOI:10.1038/nrclinonc.2009.216 · 15.70 Impact Factor