Abstract
Background
Although human epidermal growth factor receptor 2 (HER2) is a significant clinical biomarker for breast cancer, the HER2 testing involves a complicated evaluation process. We devised an easy method for HER2 gene testing and investigated its utility.
Methods
HER2 testing was performed by immunohistochemistry (IHC) and dual-color in situ hybridization (DISH) on surgical specimens from 50 patients with invasive breast cancer. DISH was evaluated by two methods. One was the DISH count method in which the HER2 and CEP17 signals were counted and the HER2/CEP17 signal ratio was calculated. The other was the DISH-easy method in which pathologists only observed slices without counting the signals. The DISH-easy method was performed by two pathologists. We analyzed the correlations between the DISH-easy method and the DISH count method by each pathologist and calculated the inter-observer concordance rate of the DISH-easy method.
Results
The results from two pathologists using the DISH-easy method corresponded to the IHC results (P < 0.01) and the DISH count method results (P < 0.01). All cases determined to be negative using the DISH-easy method were also negative via the DISH count method with a corresponding rate of 100 % for both pathologist A (34/34) and B (32/32). Most of the results for the positive cases also corresponded; the correspondence rate of pathologist A was 100 % (8/8) and 89 % for B (8/9). The inter-observer concordance rate was 81 % (κ = 0.65).
Conclusions
The DISH-easy method is simple and useful for HER2 testing regardless of proficiency of the evaluators.
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References
Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2002;20(3):719–26.
Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007;25(1):118–45. doi:10.1200/JCO.2006.09.2775.
Egervari K, Szollosi Z, Nemes Z, Kaczur V. Comparison of immunohistochemical and fluorescence in situ hybridization assessment of HER-2 status in routine practice. Am J Clin Pathol. 2006;125(1):155–6.
Ross JS, Slodkowska EA, Symmans WF, Pusztai L, Ravdin PM, Hortobagyi GN. The HER-2 receptor and breast cancer: 10 years of targeted anti-HER-2 therapy and personalized medicine. Oncologist. 2009;14(4):320–68 doi:10.1634/theoncologist.2008-0230.
Cuadros M, Villegas R. Systematic review of HER2 breast cancer testing. Appl Immunohistochem Mol Morphol. 2009;17(1):1–7. doi:10.1097/PAI.0b013e318169fc1c.
Horii R, Matsuura M, Iwase T, Ito Y, Akiyama F. Comparison of dual-color in situ hybridization and fluorescence in situ hybridization in HER2 gene amplification in breast cancer. Breast Cancer. 2013. doi:10.1007/s12282-012-0436-0.
Brügmann A, Lelkaitis G, Nielsen S, Jensen KG, Jensen V. Testing HER2 in breast cancer: a comparative study on BRISH, FISH, and IHC. Appl Immunohistochem Mol Morphol. 2011;19(3):203–11. doi:10.1097/PAI.0b013e3181f7118e.
Bartlett JM, Campbell FM, Ibrahim M, O’Grady A, Kay E, Faulkes C, et al. A UK NEQAS ISH multicenter ring study using the Ventana HER2 dual-color ISH assay. Am J Clin Pathol. 2011;135(1):157–62. doi:10.1309/AJCPVPRKK1ENEDGQ.
García-García E, Gómez-Martín C, Angulo B, Conde E, Suárez-Gauthier A, Adrados M, et al. Hybridization for human epidermal growth factor receptor 2 testing in gastric carcinoma: a comparison of fluorescence in situ hybridization with a novel fully automated dual-colour silver in situ hybridization method. Histopathology. 2011;59(1):8–17. doi:10.1111/j.1365-2559.2011.03894.x.
Nitta H, Hauss-Wegrzyniak B, Lehrkamp M, Murillo AE, Gaire F, Farrell M, et al. Development of automated brightfield double in situ hybridization (BDISH) application for HER2 gene and chromosome 17 centromere (CEN 17) for breast carcinomas and an assay performance comparison to manual dual color HER2 fluorescence in situ hybridization (FISH). Diagn Pathol. 2008;3:41 1746-1596-3-41.
Koh YW, Lee HJ, Lee JW, Kang J, Gong G. Dual-color silver-enhanced in situ hybridization for assessing HER2 gene amplification in breast cancer. Mod Pathol. 2011;24(6):794–800 doi:10.1038/modpathol.2011.9.
Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med. 2007;131(1):18–43. doi:10.1043/1543-2165(2007)131[18:ASOCCO]2.0.CO;2.
Rosenberg CL. Polysomy 17 and HER-2 amplification: true, true, and unrelated. J Clin Oncol. 2008;26(30):4856–8 doi:10.1200/JCO.2008.17.2684.
Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer. American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. Arch Pathol Lab Med. 2014;138(2):241–56. doi:10.5858/arpa.2013-0953-SA (Epub 2013 Oct 7).
Acknowledgments
This study was supported in part by Roche Diagnostics K.K. (Tokyo, Japan). We thank Ms. Tomoyo Kakita, Ms. Mayumi Ogawa, Mr. Genkichi Iwakoshi and the technical staff of the Department of Pathology, Cancer Institute, for their excellent technical support.
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The authors declare that they have no conflict of interest.
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Nakagawa, T., Horii, R., Ito, Y. et al. Development of an easy method to test for HER2 in breast cancer using dual-color in situ hybridization. Breast Cancer 23, 78–84 (2016). https://doi.org/10.1007/s12282-014-0533-3
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DOI: https://doi.org/10.1007/s12282-014-0533-3