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

Authors

  • Magdalena Bogdanovska-Todorovska Institute of Pathology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
  • Slavica Kostadinova-Kunovska Institute of Pathology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
  • Rubens Jovanovik Institute of Pathology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
  • Blagica Krsteska Institute of Pathology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
  • Goran Kondov University Clinic for Thoracic and Vascular Surgery, Clinical Centre “Mother Theresa”, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
  • Borislav Kondov University Clinic for Thoracic and Vascular Surgery, Clinical Centre “Mother Theresa”, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
  • Gordana Petrushevska Institute of Pathology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia

DOI:

https://doi.org/10.3889/oamjms.2018.124

Keywords:

Breast cancer, HER – 2, Fluorescence in situ hybridisation, Immunohistochemistry

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.

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References

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

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

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

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

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

Dowsett M, Hanna WM, Kockx M, Penault-Llorca F, Ruschoff J, Gutjahr T, et al. Standardization of HER2 testing: Results of an international proficiency-testing ring study. Mod Pathol. 2007; 20(5):584-591. https://doi.org/10.1038/modpathol.3800774 PMid:17396141

Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, 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(31):3997-4013. https://doi.org/10.1200/JCO.2013.50.9984 PMid:24101045

Perez EA, Cortes J, Gonzalez-Angulo AM, Bartlett JM. HER2 testing: Current status and future directions. Cancer Treat Rev. 2014; 40(2):276-284. https://doi.org/10.1016/j.ctrv.2013.09.001 PMid:24080154

Schnitt SJ, Jacobs TW. Current status of HER2 testing: caught between a rock and a hard place. Am J Clin Pathol. 2001; 116(6):806-810. https://doi.org/10.1309/WMN8-VTR5-DUGF-X12L PMid:11764067

Gokhale S, Gatalica Z, Mohammad A, Rampy AI, Velagaleti Gopalrao VN. FISH for HER-2/neu in breast cancer: Standardization makes the difference! Indian J Cancer. 2004; 41(4):152-158. PMid:15659867

Elston CW, Ellis IO: Pathological prognostic factors in breast cancer I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991; 19(5):403-410. https://doi.org/10.1111/j.1365-2559.1991.tb00229.x PMid:1757079

Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A eds. AJCC Cancer Staging Handbook. 7th ed. New York: Springer-Verlag, 2010.

Anderson E. The role of oestrogen and progesterone receptors in human mammary development and tumorigenesis. Breast Cancer Res. 2002; 4(5):197-201. https://doi.org/10.1186/bcr452 PMid:12223124 PMCid:PMC138744

Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thurlimann B, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol. 2013; 24(9):2206-2223. https://doi.org/10.1093/annonc/mdt303 PMid:23917950 PMCid:PMC3755334

Bogdanovska-Todorovska M, Petrushevska G, Janevska V, Spasevska L, Kostadinova-Kunovska S. Standardization and optimization of fluorescence in situ hybridization (FISH) for HER-2 assessment in breast cancer: A single center experience. Bosnian journal of basic medical sciences. 2018 Jan 30. https://doi.org/10.17305/bjbms.2018.2519 PMid:29389309

Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001; 94(2):153-156. https://doi.org/10.1002/ijc.1440 PMid:11668491

Gong Y, Sweet W, Duh YJ, Greenfield l, Fang Y, Zhao J, et al. Chromogenic in situ hybridization is a reliable method for detecting HER2 gene status in breast cancer. Am. J. Clin. Pathol. 2009; 131(4): 490-497. https://doi.org/10.1309/AJCPI00TVGIGYXAA PMid:19289584

Slamon D, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against Her-2 for metastatic breast cancer that overexpresses Her-2. N Engl J Med. 2001; 344(11):783–792. https://doi.org/10.1056/NEJM200103153441101 PMid:11248153

Ellis CM, Dyson MJ, Stephenson TJ, Maltby EL. HER2 amplification status in breast cancer: a comparison between immunohistochemical staining and fluorescence in situ hybridisation using manual and automated quantitative image analysis scoring techniques. J Clin Pathol. 2005; 58(7):710–714. https://doi.org/10.1136/jcp.2004.023424 PMid:15976337 PMCid:PMC1770709

Bilous M, Dowsett M, Hanna W et al. Current Perspectives on HER2 Testing: A Review of National Testing Guidelines. Mod Pathol. 2003; 16(2):173–182. https://doi.org/10.1097/01.MP.0000052102.90815.82 PMid:12591971

Hammock L, Lewis M, Phillips C, Cohen C. Strong HER-2/neu Protein Overexpression by Immunohistochemistry Often Does Not Predict Oncogene Ampliï¬cation by Fluorescence In Situ Hybridization. Hum Pathol. 2003; 34(10):1043-1047. https://doi.org/10.1053/S0046-8177(03)00409-X

Nitta H, Kelly BD, Allred C, Jewell S, Banks P, Dennis E, Grogan TM. The assessment of HER2 status in breast cancer: the past, the present, and the future. Pathol Int. 2016; 66(6):313–324. https://doi.org/10.1111/pin.12407 PMid:27061008

Pauletti G, Dandekar S, Rong H, Ramos L, Peng H, Seshadri R, Slamon DJ. Assessment of methods for tissue-based detection of the HER-2/neu alteration in human breast cancer: A direct comparison of fluorescence in situ hybridization and immunohistochemistry. J Clin Oncol. 2000; 18(21):3651-64. https://doi.org/10.1200/JCO.2000.18.21.3651 PMid:11054438

Lebeau A, Deimling D, Kaltz C, Sendelhofert A, Iff A, Luthardt B, et al. HER-2/neu analysis in archival tissue samples of human breast cancer: Comparison of immunohistochemistry and fluorescence in situ hybridization. J Clin Oncol. 2001; 19(2):354-363. https://doi.org/10.1200/JCO.2001.19.2.354 PMid:11208826

Tubbs RR, Pettay JD, Roche PC, Stoler MH, Jenkins RB, GroganTM. Discrepancies in clinical laboratory testing of eligibility for trastuzumab therapy: Apparent immunohistochemical false-positives do not get the message. J Clin Oncol. 2001; 19(10):2714-2721. https://doi.org/10.1200/JCO.2001.19.10.2714 PMid:11352964

Perez EA, Roche PC, Jenkins RB, Reynolds CA, Halling KC, Ingle JN, Wold LE. HER-2/neu testing in patients with breast cancer: Poor correlation between weak positivity by immunohistochemistry and gene ampliï¬cation by fluorescence in situ hybridization. Mayo Clin Proc. 2002; 77(2):148-154. https://doi.org/10.1016/S0025-6196(11)62329-X

Ridolï¬ RL, Jamehdor MR, Arber JM. HER-2/neu testing in breast carcinoma: A combined immunohistochemical and fluorescence in situ hybridization approach. Mod Pathol. 2000; 13(8):866-873. https://doi.org/10.1038/modpathol.3880154 PMid:10955453

Dybdal N, Leiberman G, Anderson S, McCune B, Bajamonde A, Cohen RL, et al. Determination of HER2 gene amplification by fluorescence in situ hybridization and concordance with the clinical trials immunohistochemical assay in women with metastatic breast cancer evaluated for treatment with trastuzumab. Breast Cancer Res Treat. 2005; 93(1):3-11. https://doi.org/10.1007/s10549-004-6275-8 PMid:16184453

Dendukuri N, Khetani K, McIsaac M, Brophy J. Testing for HER2-positive breast cancer: a systematic review and cost-effectiveness analysis. CMAJ. 2007; 176(10):1429–1434. https://doi.org/10.1503/cmaj.061011 PMid:17485695 PMCid:PMC1863543

Sarode VR, Xiang QD, Christie A, Collins R, Rao R, Leitch AM, et al. Evaluation of HER2/neu status by immunohistochemistry using computer-based image analysis and correlation with gene amplification by fluorescence in situ hybridization assay: A 10-year experience and impact of test standardization on concordance rate. Arch Pathol Lab Med. 2015; 139(7):922-928. https://doi.org/10.5858/arpa.2014-0127-OA PMid:26125432

Brunelli M, Manfrin E, Martignoni G, Bersani S, Remo A, Reghellin D, et al. HER-2/neu assessment in breast cancer using the original FDA and new ASCO/CAP guidelines recommendation: impact in selecting patients for Herceptin therapy. Am J Clin Pathol. 2008; 129(6):907-911. https://doi.org/10.1309/MD79CDXN1D01E862 PMid:18480007

Roche PC, Suman VJ, Jenkins RB, Davidson NE, Martino S, Kaufman PA et al. Concordance between local and central laboratory HER2 testing in the Breast Intergroup Trial N9831. J Natl Cancer Inst. 2002; 94(11):855-857. https://doi.org/10.1093/jnci/94.11.855 PMid:12048274

Ross JS, Fletcher JA, Bloom KJ, Linette GP, Stec J, Clark E, et al. Her- 2/ neu testing in breast cancer. Am J Clin Pathol. 2003; 120(Suppl 1):S53-S71. https://doi.org/10.1309/949FPQ1AQ3P0RLC0

Makar AP, Desmedt EJ, De Potter CR, Vanderheyden JS, Schatteman EA. Neu (C-erbB-2) oncogene in breast cancer and its possible association with the risk of distant metastases. A retrospective study and review of literature. Acta Oncol. 1990; 29(7):931-934. https://doi.org/10.3109/02841869009096392 PMid:1979748

Panjwani P, Epari S, Karpate A, Shirsat H, Rajsekharan P, Basak R et al. Assessment of HER-2/neu status in breast cancer using fluorescence in situ hybridization & immunohistochemistry: Experience of a tertiary cancer referral centre in India. Indian J Med Res. 2010; 132:287-294 PMid:20847375

Onody P, Bertrand F, Muzeau F, Bieche I, Lideteau R. Fluorescence In Situ Hybridization and Immunohistochemical Assays for HER-2/ neu Status Determination. Arch Pathol Lab Med. 2001; 125(6):746–750. PMid:11371225

Qiao E-Q, Ji M, Wu J, Li J, Xu X, Ma R et al. Joint detection of multiple immunohistochemical indices and clinical significance in breast cancer. Mol Clin Oncol. 2013; 1(4):703-710. https://doi.org/10.3892/mco.2013.111 PMid:24649232 PMCid:PMC3915321

Shokouh TZ, Ezatollah A, Barand P. Interrelationships Between Ki67, HER2/neu, p53, ER, and PR Status and Their Associations With Tumor Grade and Lymph Node Involvement in Breast Carcinoma Subtypes: Retrospective-Observational Analytical Study. Feng Y, ed. Medicine. 2015; 94(32):e1359.

Bartlett JM, Ellis IO, Dowsett M, Mallon EA, Cameron DA, Johnson S et al. Human epidermal growth factor receptor 2 status correlates with lymph node involvement in patients with estrogen receptor (ER) negative, but with grade in those with ER-positive early-stage breast cancer suitable for cytotoxic chemotherapy. J Clin Oncol. 2007; 25(28):4423-4430. https://doi.org/10.1200/JCO.2007.11.0973 PMid:17906205

Ali EM, Ahmed ARH, Ali AMA. Correlation of Breast Cancer Subtypes Based on ER, PR and HER2 Expression with Axillary Lymph Node Status. Cancer and Oncology Research 2014, 2(4): 51-57.

Payandeh M, Shahriari-Ahmadi A, Sadeghi1 M, Sadeghi E. Correlations between HER2 Expression and Other Prognostic Factors in Breast Cancer: Inverse Relations with the Ki-67 Index and P53 Status. Asian Pac J Cancer Prev. 2016; 17(3)1015-1018. https://doi.org/10.7314/APJCP.2016.17.3.1015 PMid:27039719

Zhou P, Jiang YZ, Hu X, Sun W, Liu RY, Liu F et al. Clinicopathological characteristics of patients with HER2-positive breast cancer and the efficacy of trastuzumab in the People's Republic of China. Onco Targets Ther. 2016; 18(9):2287-2295. https://doi.org/10.2147/OTT.S97583 PMid:27143924 PMCid:PMC4846044

Published

2018-03-22

How to Cite

1.
Bogdanovska-Todorovska M, Kostadinova-Kunovska S, Jovanovik R, Krsteska B, Kondov G, Kondov B, Petrushevska G. Correlation of Immunohistochemistry and Fluorescence in Situ Hybridization for HER-2 Assessment in Breast Cancer Patients: Single Centre Experience. Open Access Maced J Med Sci [Internet]. 2018 Mar. 22 [cited 2024 Mar. 28];6(4):593-9. Available from: https://oamjms.eu/index.php/mjms/article/view/oamjms.2018.124

Issue

Section

A - Basic Science

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