Reproducibility in the Assessment of HER2 DISH in Breast Cancer

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Tauangtham Anekpuritanang, MD
Thiamjit Chaichana, MSc
Preecha Ruangvejvorachai, MSc
Shanop Shuangshoti, MD


OBJECTIVE: HER2 gene status is an important biological marker that determines both the prognosis and response to Trastuzumab in patients with breast cancers. Although FISH assay has long been used to determine the HER2 gene copy
number, DISH is gaining popularity since it can be assessed with a conventional microscope. The DISH test relies on an individual inspection however, so inter-observer variation may be an issue.

MATERIALS AND METHODS: In the current study, reproducibility in the assessment of HER2 DISH test was evaluated in 69 breast cancer samples with HER2 IHC score 2+ and 3+. Two independent investigators evaluated the digitallycaptured images of DISH, without the knowledge of HER2 IHC status.

RESULTS: The HER2/CEP17 ratio obtained from both observers were highly correlated (Rho = 0.883, p < 0.001). Based on the ASCO 2013 guideline, agreement of both investigators for HER2 gene diagnosis was 92.75 % (ĸ = 0.848). The HER2/CEP17 ratio of the discordant cases ranged from 1.6 (non-amplifi ed HER2) to 2.6 (low level of HER2 gene amplifi cation).

CONCLUSION: It is concluded that the DISH method produces good reproducibility between independent observers, and the result also implies that the HER2 gene copy number is fairly homogenous across an individual breast cancer sample.

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How to Cite
Anekpuritanang T, Chaichana T, Ruangvejvorachai P, Shuangshoti S. Reproducibility in the Assessment of HER2 DISH in Breast Cancer. BKK Med J [Internet]. 2015 Sep. 18 [cited 2024 Apr. 23];10(1):1. Available from:
Original Article


1. Jemal A, Bray F, Center M, et al. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
2. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013;63:11-30.
3. Slamon D, Leyland-Jones B, Shak S, et al. Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2. N Engl J Med 2001;344:783-92.
4. Perez EA, Romond EH, Suman VJ, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol 2014;32:3744-52.
5. Wolff AC, Hammond ME, Hicks DG, 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. J Clin Oncol 2013;31:3997- 4013.
6. Gullo G, Bettio D, Torri V, et al. Level of HER2/neu gene amplification as a predictive factor of response to trastuzumab- based therapy in patients with HER2-positive metastatic breast cancer. Invest New Drugs 2008; 27:179-83.
7. Mansfield A, Sukov W, Eckel-Passow J, et al. Comparison of Fluorescence In Situ Hybridization (FISH) and Dual- ISH (DISH) in the Determination of HER2 Status in Breast Cancer. Am J Clin Pathol 2013;139:144-50.
8. Horii R, Matsuura M, Iwase T, et al. Comparison of dualcolor in-situ hybridization and fluorescence in-situ hybridization in HER2 gene amplification in breast cancer. Breast Cancer 2014;21:598-604.
9. Wolff A, Hammond E, Schwartz J, 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;131:18-43.
10. Cuadros M, Villegas R. Systematic review of HER2 breast cancer testing. Appl Immunohistochem Mol Morphol. 2009;17:1-7.
11. Shin SJ, Hyjek E, Early E, Knowles DM. Intratumoral heterogeneity of HER2/neu in invasive mammary carcinomas using fluorescence in-situ hybridization and tissue microarray. Int J Surg Pathol 2006;14:279-84.
12. Brunelli M, Manfrin E, Martignoni G, et al. Genotypic intratumoral heterogeneity in breast carcinoma with HER2/neu amplification: evaluation according to ASCO/ CAP criteria. Am J Clin Pathol 2009;131:678-82.
13. Hanna WM, Rüschoff J, Bilous M, et al. HER2 in situ hybridization in breast cancer: clinical implications of polysomy 17 and genetic heterogeneity. Mod Pathol 2014;27:4-18.
14. Shuangshoti S, Sawatdee R, Sakapibunnan A, et al. Heterogeneity of Unilateral Multiple Breast Cancer: Implications for Biomarker Testing. Bangkok Med J 2015;8:17-21.
15. Fuchs E, Köstler W, Horvat R, et al. High-level ERBB2 gene amplification is associated with a particularly short time-to-metastasis, but results in a high rate of complete response once trastuzumab-based therapy is offered in the metastatic setting. Int J Cancer 2014;135:224-31.