Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Mar 23;6(4):593-599.
doi: 10.3889/oamjms.2018.124. eCollection 2018 Apr 15.

Correlation of Immunohistochemistry and Fluorescence in Situ Hybridization for HER-2 Assessment in Breast Cancer Patients: Single Centre Experience

Magdalena Bogdanovska-Todorovska  1 , Slavica Kostadinova-Kunovska  1 , Rubens Jovanovik  1 , Blagica Krsteska  1 , Goran Kondov  2 , Borislav Kondov  2 , Gordana Petrushevska  1
Affiliations

Correlation of Immunohistochemistry and Fluorescence in Situ Hybridization for HER-2 Assessment in Breast Cancer Patients: Single Centre Experience

Magdalena Bogdanovska-Todorovska et al. Open Access Maced J Med Sci. .

Abstract

Background: Accurate assessment of HER-2 is imperative in selecting patients for targeted therapy. Most commonly used test methods for HER-2 are immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). We evaluated the concordance between FISH and IHC for HER-2 in breast cancer samples using Food and Drug Administration approved tests.

Material and methods: Archived paraffin tissue blocks from 73 breast cancer patients were used. HER-2 immunostaining was performed using Ventana anti-HER-2 monoclonal antibody. The FISH assay was performed using PathVysion™ HER-2 DNA Probe Kit.

Results: Of the 73 cases 68.5% were IHC 0/1+, 15.07% were IHC 2+ and 16.44% were IHC 3+. Successful hybridisation was achieved in 72 cases. HER-2 FISH amplification was determined in 16.67% cases. Ten IHC 3+ and two IHC 2+ cases were FISH positive. Two of the IHC 3+ cases were FISH negative. Concordance rate was 100%, 18.18% and 83.33% for IHC 0/1+, 2+ and 3+ group, respectively. Total concordance was 84.72%, kappa 0.598 (p < 0.0001). The sensitivity of IHC in detecting IHC 2+ and IHC 3+ cases was 16.7% and 83.3%, and the specificity was 85% and 96.67%, respectively.

Conclusion: The consistency between the methods was highest for IHC negative and lowest for IHC equivocal cases. The immunohistochemistry showed high sensitivity for IHC 2+/3+ cases and high specificity for IHC 3+ cases. Our results support the view that false-positive rather than false-negative IHC results are a problem with HER-2/IHC testing, and that IHC should be used as an initial screening test, but IHC 2+/ 3+ results should be confirmed by FISH.

Keywords: Breast cancer; Fluorescence in situ hybridisation; HER –2; Immunohistochemistry.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Distribution of HER-2 according to A, IHC (left) and B, FISH (right)
Figure 2
Figure 2
Typical examples of FISH-positive and FISH negative case. A, FISH amplified case, HER-2/Chr 17>2 (DAPI counterstain x 1000); B, FISH non amplified case, HER-2/Chr 17 < 2 (DAPI counterstain x 1000)
Figure 3
Figure 3
Discordance between IHC and FISH in two cases. Case 1: A, Invasive breast carcinoma (H&E x 200); B, HER-2/IHC 3+ (HER-2 x 200), C, FISH, HER-2/Chr 17 < 2, non amplified (DAPI counterstain x 1000). Case 2: D, Invasive breast carcinoma (H&E x 200); E, HER-2/IHC 3+ (HER-2 x 200); F, FISH, HER-2/Chr 17 < 2, non-amplified (DAPI counterstain x 1000)
See this image and copyright information in PMC

References

    1. Ross JS, Slodkowska EA, Symmans WF, Pusztai L, Ravdin PM, Hortobagyi GN. The HER-2 receptor and breast cancer: Ten years of targeted anti-HER-2 therapy and personalised medicine. Oncologist. 2009;14(4):320–368. https://doi.org/10.1634/theoncologist.2008-0230. PMid:19346299. - PubMed
    1. Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Richard 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(1):18–43. PMid:19548375. - PubMed
    1. Sauter G, Lee J, Bartlett JM, Slamon DJ, Press MF. Guidelines for human epidermal growth factor receptor 2 testing: Biologic and methodologic considerations. J Clin Oncol. 2009;27(8):1323–1333. https://doi.org/10.1200/JCO.2007.14.8197. PMid:19204209. - PubMed
    1. Sapino A, Goia M, Recupero D, Marchiò C. Current challenges for HER2 testing in diagnostic pathology: State of the art and controversial issues. Front Oncol. 2013;3:129. https://doi.org/10.3389/fonc.2013.00129. PMid:23734345. PMCid: PMC3659312. - PMC - PubMed
    1. Lottner C, Schwarz S, Diermeier S, Hartmann A, Knuechel R, Hofstaedter F, et al. Simultaneous detection of HER2/neu gene amplification and protein overexpression in paraffin-embedded breast cancer. J Pathol. 2005;205(5):577–584. https://doi.org/10.1002/path.1742. PMid:15732132. - PubMed

LinkOut - more resources