Comparison of Immunohistochemical and Fluorescence In Situ Hybridization Assessment of HER-2 Status in Routine Practice

Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
American Journal of Clinical Pathology (Impact Factor: 2.51). 06/2005; 123(5):766-70. DOI: 10.1309/Q0DG-L26R-UCK1-K5EV
Source: PubMed


Because HER-2 expression in invasive carcinoma of the breast has well-documented ramifications for treatment and prognosis, accurate assessment of HER-2 status is critical. Comparative studies have shown high concordance rates between immunohistochemical analysis and fluorescence in situ hybridization (FISH) in cases with immunohistochemical scores of 0 or 1+ (negative) and 3+ (strongly positive) and low concordance rates among cases with immunohistochemical scores of 2+. The present study was performed to determine concordance rates in a setting more representative of routine clinical practice, in which multiple pathologists submit specimens to a single cytogenetics referral laboratory. We found a higher rate of discordance between immunohistochemical analysis and FISH (approximately 92%) in the groups with immunohistochemical scores of 2+ than reported in other studies. These results strongly support the practice of performing FISH in all cases with immunohistochemical scores of 2+, particularly in routine practice, in which interobserver variability in immunohistochemical scoring among multiple pathologists is likely to be high.

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Available from: Michelle Dolan, Dec 18, 2013
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    • "HER2 immunohistochemistry (IHC) and HER2 fluorescence in situ hybridization (FISH) are well-established tests for determining HER2 amplification status [8] [9] [10] [11] [12]. Given the importance of these tests in guiding the decision to treat with HER2-targeted therapeutics, periodic institutional review of HER2 IHC and HER2 FISH reporting is warranted in an effort to maintain high concordance and low interobserver variability [1] [8] [9] [10] [11] [12] [13] [14] [15] [16]. As such, the College of American Pathologists Accreditation Checklist requires comparison of laboratory predictive results with published benchmarks; however, there is no requirement for analysis of the results of individual pathologists [17]. "
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    ABSTRACT: The College of American Pathologists Accreditation Checklist requires comparison of laboratory predictive results with published benchmarks but does not require analysis of individual pathologists. With the availability of targeted human epidermal growth factor receptor 2 (HER2) protein therapy, uniform reporting of HER2 protein status by immunohistochemistry (IHC) is essential. Our aim was to compare HER2 IHC results among pathologists in routine clinical practice within a single institution and assess the impact of simultaneous IHC and fluorescence in situ hybridization (FISH) ordering. We reviewed reports from 928 consecutive breast needle biopsies from 2008 to 2012 at a tertiary academic medical center in which HER2 IHC and HER2 FISH were ordered. There was a significant association between breast pathologist and IHC result (negative, 49.8%-83.2%; positive, 8.7%-14.1%; equivocal, 5.2%-41.5%; P < .0001) but not breast pathologist and FISH result (P = .69). For 1 pathologist, IHC signed out with FISH had an equivocal rate nearly 2-fold lower than IHC results that were reported first (10.5% versus 20.9%) (P = .04). Institutions should be aware that although overall HER2 IHC reporting may be consistent with guidelines, there can be significant variation among practitioners. In addition to aggregate data, we recommend comparing the rates from individual pathologists to standards. Furthermore, routine simultaneous ordering of both IHC and FISH could impact interpretation of test results and may inappropriately encourage less confidence in IHC results among pathologists.
    Full-text · Article · Sep 2015 · Human pathology
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    • "They also concluded that FISH can be an additional, complementary method to detect false negative IHC results, especially those with a high degree of malignancy. A study by Dolan and Snover [23] showed that the concordance rate between FISH and IHC results is 27.1%. Lan et al. [24] documented amplification of the HER2 gene with the FISH method in only 96 out of 221 cases of breast cancer, and found that the concordance rate of the two methods is 44.4%. "
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    ABSTRACT: The HER2 gene is responsible for the formation of the HER2 receptor on the surface of epithelial cells. Increased numbers of this receptor are associated with a worse prognosis in cancer. Increased numbers of copies of the HER2 gene occur in about 20-30% of breast cancer patients, so determining HER2 receptor levels is important in the current diagnosis and treatment of breast cancer. One diagnostic technique is the immunohistochemical (IHC) method, which permits indirect measurement of overexpression of HER2 receptors, based on subjective determination of the intensity of the color reaction. Another technique is the use of fluorescent in situ hybridization (FISH), which permits the exact number of copies of the HER2 gene to be specified. Based on the results of FISH tests, patients can be qualified for treatment with antibodies that partially block HER2 receptors. This treatment causes inhibition of tumor growth signals. Determining the HER2 status in breast cancer with the FISH method allows the further progress of the disease to be predicted, the right treatment to be chosen and the response to the treatment to be foreseen. Because of the widespread use of the FISH and IHC methods, comparing the advantages and disadvantages of these two methods seems to be relevant.
    Preview · Article · Jan 2015 · Advances in Clinical and Experimental Medicine
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    • "1% ) and discordance in 94 cases ( 72 . 9% ) ( Dolan and Snover , 2005 "
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    ABSTRACT: The concordance rate between immunohistochemical (IHC) and fluorescence in situ hybridization (FISH) results for HER2/neu according to clinical performance is controversial. The present prospective study was theerefore conducted in Indian breast cancer patients. Fifty cases (n=50) of invasive duct cancer of breast tested for HER-2/neu by IHC and scored as 0, 1+, 2+ and 3+ by pathologists were further analyzed by FISH using a commercially available double-color probe, and the findings compared. A total concordance of 82.0% was observed with a Kappa coefficient of 0.640 (P <0.001). A high discordance was observed in 30.0% of the patients with IHC 2+, 7.1% in IHC 3+, 19.2% overall in IHC 0 and 1+. IHC can be used firstly to screen the HER-2/neu status, and FISH can be used as a supplementary role to IHC and 2+ and some negative cases. And only those cases with HER-2/neu status of IHC 3+ or FISH positive should be treated with Herceptin (Trastuzumab).
    Preview · Article · Jan 2011 · Asian Pacific journal of cancer prevention: APJCP
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