Breast Cancer

, Volume 22, Issue 6, pp 615–625 | Cite as

A meta-analysis on concordance between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) to detect HER2 gene overexpression in breast cancer

  • Fatemeh Bahreini
  • Ali Reza Soltanian
  • Parvin MehdipourEmail author
Original Article



We performed this meta-analysis study to evaluate the concordance and discordance between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in detecting HER2 alteration in human breast cancer.


As a meta-analysis, the present study evaluated the available data from previous studies on the HER2 gene detected by IHC and FISH. To indicate the meta-analysis results, a forest plot was used.


We identified 172 citations, for which our inclusion criteria were met by 18 articles, representing 6629 cases. The overall concordance and discordance rate between IHC staining with score 0/1+ and FISH for detection failure of HER2 expression was 96 and 4 %, respectively. The present study showed that the overall proportion of FISH positive and negative rate for IHC score 2+ for detection of HER2 expression was 36 and 64 %, respectively; and 91 and 9 % for 3+ IHC scores.


The results of this study show that IHC score 0/1+ and 3+ cannot be completely considered as negative and positive breast cancer test, respectively. Therefore, we suggest a valid and complementary test, the same as FISH, to explore HER2 expression.


HER2 Immunohistochemistry Fluorescence in situ hybridization Breast cancer Meta-analysis 



We thank the editorial boards and reviewers for editorial assistance with this manuscript.

Conflict of interest

P. Mehdipour, F. Bahreini, and A. R. Soltanian have nothing to disclose.


  1. 1.
    Pauletti G, Dandekar S, Rong H, Ramos L, et al. 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.PubMedGoogle Scholar
  2. 2.
    Muss HB, Thor-Ann D, Berry-Donald A, et al. C-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med. 1994;330:1260–6.CrossRefPubMedGoogle Scholar
  3. 3.
    Soonmyung P, John B, Chanheun P, et al. ErbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer. J Natl Cancer Inst. 1998;90(18):1361–70.CrossRefGoogle Scholar
  4. 4.
    Eichhorn Pieter JA, José B. HER2 Signatures in breast cancer: ready to go to print? Am Soc Clin Oncol. 2010;28(11):1809–10.CrossRefGoogle Scholar
  5. 5.
    Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244(4905):707–12.CrossRefPubMedGoogle Scholar
  6. 6.
    Dowsett M, Bartlett J, Ellis IO, et al. Correlation between immunohistochemistry (HercepTest) and fluorescence in situ hybridization (FISH) for HER-2 in 426 breast carcinomas from 37 centers. J Pathol. 2003;199:418–23.CrossRefPubMedGoogle Scholar
  7. 7.
    Perez Edith A, Roche Patrick C, Jenkins Robert B, et al. HER2 testing in patients with breast cancer: poor correlation between weak positivity by immunohistochemistry and gene amplification by fluorescence in situ hybridization. Mayo Clin Proc. 2002;77:148–54.CrossRefPubMedGoogle Scholar
  8. 8.
    Rhodes A, Sarson J, Assam E, et al. The reliability of rabbit monoclonal antibodies in the immunohistochemical assessment of estrogen receptors, progesterone receptors, and HER2 in human breast carcinomas. Am Soc Clin Pathol. 2010;134:621–32.CrossRefGoogle Scholar
  9. 9.
    Alkushi A. Validation of tissue microarray biomarker expression of breast carcinomas in Saudi women. Hematol Oncol Stem Cell Ther. 2009;2(3):394–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Arens N, Bleyl U, Hildenbrand R. HER2/neu, p53, Ki67, and hormone receptors do not change during neoadjuvant chemotherapy in breast cancer. Virchows Arch. 2005;446:489–96.CrossRefPubMedGoogle Scholar
  11. 11.
    Artufel MV, Valero AC, Lladó RR, et al. Molecular protocol for HER2/neu analysis in breast carcinoma. Clin Transl Oncol. 2005;7(11):504–11.CrossRefPubMedGoogle Scholar
  12. 12.
    Bánkfalvi A, Boecker W, Reiner A. Comparison of automated and manual determination of HER2 status in breast cancer for diagnostic use: a comparative methodological study using the Ventana BenchMark automated staining system and manual tests. Int J Oncol. 2004;25(4):929–35.PubMedGoogle Scholar
  13. 13.
    Barberis M, Pellegrini C, Cannone M, et al. Quantitative PCR and HER2 testing in breast cancer. Am J Clin Pathol. 2008;1(29):563–70.CrossRefGoogle Scholar
  14. 14.
    Bishop JW, Marcelpoil R, Schmid J. Machine scoring of Her2/neu immunohistochemical stains. Anal Quant Cytol Histol. 2002;24(5):257–62.PubMedGoogle Scholar
  15. 15.
    Bouché O, Penault-Llorca F. HER2 and gastric cancer: a novel therapeutic target for trastuzumab. Bull Cancer. 2010;97(12):1429–40.PubMedGoogle Scholar
  16. 16.
    Burgea CN, Changb HR, Apple SK. Do the histologic features and results of breast cancer biomarker studies differ between core biopsy and surgical excision specimens? Breast. 2006;15:167–72.CrossRefGoogle Scholar
  17. 17.
    Carlsson J, Nordgren H, Sjostrom J, et al. HER2 expression in breast cancer primary tumours and corresponding metastases. Original data and literature review. Br J Cancer. 2004;90:2344–8.PubMedCentralPubMedGoogle Scholar
  18. 18.
    Saranya C, Stacie J, Lisa J, et al. Pathologic complete response to preoperative sequential doxorubicin/cyclophosphamide and single-agent taxane with or without trastuzumab in stage II/III HER2-positive breast cancer. Clin Breast Cancer. 2010;10(1):40–5.CrossRefGoogle Scholar
  19. 19.
    Conlin AK, Seidman AD, Bach A, et al. Phase II trial of weekly nanoparticle albumin-bound paclitaxel with carboplatin and trastuzumab as first-line therapy for women with HER2-overexpressing metastatic breast cancer. Clin Breast Cancer. 2010;10(4):281–7.CrossRefPubMedGoogle Scholar
  20. 20.
    Dank M. Human recombinant anti-HER2 monoclonal antibody—a new targeted treatment in breast cancer. Orv Hetil. 2001;142(46):2563–8.PubMedGoogle Scholar
  21. 21.
    Shaheenah D, Gonzalez-Angulo Ana M, Florentia P, et al. Efficacy and safety of neoadjuvant trastuzumab combined with paclitaxel and epirubicin. Cancer. 2007;110(6):1195–200.CrossRefGoogle Scholar
  22. 22.
    Raihanatou D, Karl-Ludwig S, Agnes B, et al. Secretory carcinoma of the breast: a distinct variant of invasive ductal carcinoma assessed by comparative genomic hybridization and immunohistochemistry. Hum Pathol. 2003;34(12):1299–305.CrossRefGoogle Scholar
  23. 23.
    Erinn DK, Brian JY, Mark S, et al. The influence of polysomy 17 on HER2 gene and protein expression in adenocarcinoma of the breast. Am J Surg Pathol. 2005;29:1221–7.CrossRefGoogle Scholar
  24. 24.
    Dowsett M, Procter M, McCaskill-Stevens W, et al. Disease-free survival according to degree of HER2 amplification for patients treated with adjuvant chemotherapy with or without 1 year of trastuzumab: the HERA trial. J Clin Oncol. 2009;27:2962–9.PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    Egervari K, Szollosi Z, Nemes Z. Immunohistochemical antibodies in breast cancer HER2 diagnostics. A comparative immunohistochemical and fluorescence in situ hybridization study. Tumour Biol. 2008;29(1):18–27.CrossRefPubMedGoogle Scholar
  26. 26.
    Kristof E, Zoltan S, Zoltan N. Re: a new rabbit monoclonal antibody (4B5) for the immunohistochemical (IHC) determination of the HER2 status in breast cancer: comparison with CB11, fluorescence in situ hybridization (FISH), and interlaboratory reproducibility. Appl Immunohistochem Mol Morphol. 2008;16(5):510–1.CrossRefGoogle Scholar
  27. 27.
    Kristof E, Zoltan S, Zoltan N. Tissue microarray technology in breast cancer HER2 diagnostics. Pathol Res Pract. 2007;203:169–77.CrossRefGoogle Scholar
  28. 28.
    Fitzgibbons PL, Murphy DA, Dorfman DM, et al. Interlaboratory comparison of immunohistochemical testing for HER2. Arch Pathol Lab Med. 2006;130:1440–5.PubMedGoogle Scholar
  29. 29.
    Yimin G, Nour S, Eltorky MA, et al. Immunohistochemical characterization of subtypes of male breast carcinoma. Breast Cancer Res. 2010;11(3):1–8.Google Scholar
  30. 30.
    Hanley KZ, Birdsong GG, Cohen C, et al. Immunohistochemical detection of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression in breast carcinomas. Cancer Cytopathol. 2009;117:279–88.CrossRefGoogle Scholar
  31. 31.
    Hayes DF, Thor AD, Dressler LG, et al. HER2 and response to paclitaxel in node-positive breast cancer. N Engl J Med. 2007;357:1496–506.CrossRefPubMedGoogle Scholar
  32. 32.
    Ivković-Kapicl T, Knezević-Usaj S. Human epidermal growth factor receptor 2 testing in breast cancer. Med Pregl. 2010;63(1–2):69–74.CrossRefPubMedGoogle Scholar
  33. 33.
    Jørgensen JT, Møller S, Rasmussen BB, et al. High concordance between two companion diagnostics tests: a concordance study between the HercepTest and the HER2 FISH pharmDx kit. Am J Clin Pathol. 2011;136(1):145–51.CrossRefPubMedGoogle Scholar
  34. 34.
    Kounelis S, Kapranos N, Malamos N, et al. Evaluation of HER2 gene status in breast cancer by chromogenic in situ hybridization: comparison with immunohistochemistry. Anticancer Res. 2005;25(2A):939–46.PubMedGoogle Scholar
  35. 35.
    Kovacs A, Stenman G. HER2-testingin 538 consecutive breast cancer cases using FISH and immunohistochemistry. Pathol Res Pract. 2010;206:39–42.CrossRefPubMedGoogle Scholar
  36. 36.
    Latta EK, Tjan S, Parkes RK, et al. The role of HER2/neu overexpression/amplification in the progression of ductal carcinoma in situ to invasive carcinoma of the breast. Mod Pathol. 2002;15(12):1318–25.CrossRefPubMedGoogle Scholar
  37. 37.
    Lewis F, Jackson P, Lane S, et al. Testing for HER2 in breast cancer. Histopathology. 2004;45:207–17.CrossRefPubMedGoogle Scholar
  38. 38.
    Lidgren M, Jonsson B, Rehnberg C, et al. Cost-effectiveness of HER2 testing and 1-year adjuvant trastuzumab therapy for early breast cancer. Ann Oncol. 2008;19:487–95.CrossRefPubMedGoogle Scholar
  39. 39.
    Liu JJ, Shen R, Chen L, et al. Piwil2 is expressed in various stages of breast cancers and has the potential to be used as a novel biomarker. Int J Clin Exp Pathol. 2010;3(4):328–37.PubMedCentralPubMedGoogle Scholar
  40. 40.
    Liu YH, Xu FP, Rao JY, et al. Justification of the change from 10% to 30% for the immunohistochemical HER2 scoring criterion in breast cancer. Am J Clin Pathol. 2009;132:74–9.CrossRefPubMedGoogle Scholar
  41. 41.
    López-Guerrero JA, Navarro S, Noguera R, et al. Histological tumor grade correlates with HER2/c-erB-2 status in invasive breast cancer: a comparative analysis between immunohistochemical (CB11 clone and Herceptest), FISH and differential PCR procedures. Arkh Patol. 2003;65(1):50–5.PubMedGoogle Scholar
  42. 42.
    Loring P, Cummins R, O’Grady A, et al. HER2 positivity in breast carcinoma: a comparison of chromogenic in situ hybridization with fluorescence in situ hybridization in tissue microarrays, with targeted evaluation of intratumoral heterogeneity by in situ hybridization. Appl Immunohistochem Mol Morphol. 2005;13(2):194–200.CrossRefPubMedGoogle Scholar
  43. 43.
    Manion E, Hornick JL, Lester SC, et al. A comparison of equivocal immunohistochemical results with anti- HER2/neu antibodies A0485 and SP3 with corresponding FISH results in routine clinical practice. Am J Clin Pathol. 2011;135(6):845–51.CrossRefPubMedGoogle Scholar
  44. 44.
    Miguel M, Alvaro RL, Amparo R, et al. Molecular predictors of efficacy of adjuvant weekly paclitaxel in early breast cancer. Breast Cancer Res Treat. 2010;123:149–57.CrossRefGoogle Scholar
  45. 45.
    Morelle M, Haslé E, Treilleux I, et al. Cost-effectiveness analysis of strategies for HER2 testing of breast cancer patients in France. Int J Technol Assess Health Care. 2006;22(3):396–401.CrossRefPubMedGoogle Scholar
  46. 46.
    Ni R, Mulligan AM, Have C, et al. PGDS, a novel technique combining chromogenic in situ hybridization and immunohistochemistry for the assessment of ErbB2 (HER2/neu) status in breast cancer. Appl Immunohistochem Mol Morphol. 2007;15:316–24.CrossRefPubMedGoogle Scholar
  47. 47.
    Ogrady A, Allen D, Happerfield L, et al. An immunohistochemical and fluorescence in situ hybridization-based comparison between the OracleHER2 bond immunohistochemical system, Dako HercepTest, and Vysis PathVysion HER2 FISH using both commercially validated and modified ASCO/CAP and United Kingdom HER2 IHC scoring guidelines. Appl Immunohistochem Mol Morphol. 2010;18:489–93.CrossRefGoogle Scholar
  48. 48.
    Palacios J, Honrado E, Osorio A, et al. Phenotypic characterization of BRCA1 and BRCA2 tumors based in a tissue microarray study with 37 immunohistochemical markers. Breast Cancer Res Treat. 2005;90:5–14.CrossRefPubMedGoogle Scholar
  49. 49.
    Penault-Liorca F, Bilous M, Dowsett M, et al. Emerging technologies for assessing HER2 amplification. Am J Clin Pathol. 2009;132:539–48.CrossRefGoogle Scholar
  50. 50.
    Pritchard KI, Shepherd LE, O’Malley FP, et al. HER2 and responsiveness of breast cancer to adjuvant chemotherapy. N Engl J Med. 2006;354:2103–11.CrossRefPubMedGoogle Scholar
  51. 51.
    Ratcliffe N, Wells W, Wheeler K, et al. The combination of in situ hybridization and immunohistochemical analysis: an evaluation of Her2/neu expression in paraffin embedded breast carcinomas and adjacent normal-appearing breast epithelium. Mod Pathol. 1997;10(12):1247–52.PubMedGoogle Scholar
  52. 52.
    Socorro-Marıa RP, Yolanda RG, Gema MB, et al. Sporadic invasive breast carcinomas with medullary features display a basal-like phenotype. Am J Surg Pathol. 2007;31:501–8.CrossRefGoogle Scholar
  53. 53.
    Rody A, Karn T, Gätje R, et al. Gene expression profiles of breast cancer obtained from core cut biopsies before neoadjuvant docetaxel, adriamycin, and cyclophosphamide chemotherapy correlate with routine prognostic markers and could be used to identify predictive signatures. Zentralbl Gynakol. 2006;128(2):76–81.CrossRefPubMedGoogle Scholar
  54. 54.
    Ryden L, Haglund M, Bendahl PO, et al. Reproducibility of human epidermal growth factor receptor 2 analysis in primary breast cancer: a National survey performed at pathology departments in Sweden. Acta Oncol. 2009;48:860–6.PubMedGoogle Scholar
  55. 55.
    Ryden L, Jirstrom K, Haglund M, et al. Epidermal growth factor receptor and vascular endothelial growth factor receptor 2 are specific biomarkers in triple-negative breast cancer. Results from a controlled randomized trial with long-term follow-up. Breast Cancer Res Treat. 2010;120:491–8.CrossRefPubMedGoogle Scholar
  56. 56.
    Schaller G, Evers K, Papadopoulos S, et al. Current use of HER2 tests. Ann Oncol. 2001;12(1):S97–100.CrossRefPubMedGoogle Scholar
  57. 57.
    Shabaik A, Lin G, Peterson M, et al. Reliability of Her2/neu, estrogen receptor, and progesterone receptor testing by immunohistochemistry on cell block of FNA and serous effusions from patients with primary and metastatic breast carcinoma. Diagn Cytopathol. 2011;39(5):328–32.CrossRefPubMedGoogle Scholar
  58. 58.
    Striebel JM, Bhargava R, Horbinski C, et al. The equivocally amplified HER2 FISH result on breast core biopsy: indications for further sampling do affect patient management. Am J Clin Pathol. 2008;129(3):383–90.CrossRefPubMedGoogle Scholar
  59. 59.
    Thor A. HER2 a discussion of testing approaches in the USA. Ann Oncol. 2001;12(1):S101–7.CrossRefPubMedGoogle Scholar
  60. 60.
    Vlasoff DM, Baschinsky DY, De Young BR, et al. C-erb B2 (Her2/neu) is neither overexpressed nor amplified in hepatic neoplasms. Appl Immunohistochem Mol Morphol. 2002;10(3):237–41.PubMedGoogle Scholar
  61. 61.
    Carlson RW, Moench SJ, Hammond ME, et al. HER2 testing in breast cancer: NCCN Task Force report and recommendations. JNCCN. 2006;4(3):S1–22.Google Scholar
  62. 62.
    Cho EY, Srivastava A, Park K, et al. Comparison of four immunohistochemical tests and FISH for measuring HER2 expression in gastric carcinomas. Pathology. 2012;44(3):216–20.CrossRefPubMedGoogle Scholar
  63. 63.
    Fountzilas G, Dafni U, Bobos M, et al. Differential response of immunohistochemically defined breast cancer subtypes to anthracycline-based adjuvant chemotherapy with or without paclitaxel. PLoS ONE. 2012;7(6):e37946.PubMedCentralCrossRefPubMedGoogle Scholar
  64. 64.
    Jacobs TW, Gown AM, Yaziji H, et al. Comparison of fluorescence in situ hybridization and immunohistochemistry for the evaluation of HER-2/neu in breast cancer. J Clin Oncol. 1999;17(7):1974–80.PubMedGoogle Scholar
  65. 65.
    Kakar S, Puangsuvan N, Stevens JM, et al. HER-2/neu assessment in breast cancer by immunohistochemistry and fluorescence in situ hybridization: comparison of results and correlation with survival. Mol Diagn. 2000;5(3):199–207.CrossRefPubMedGoogle Scholar
  66. 66.
    Lambein K, Praet M, Forsyth R, et al. Relationship between pathological features, HER2 protein expression and HER2 and CEP17 copy number in breast cancer: biological and methodological considerations. J Clin Pathol. 2011;64(3):200–7.CrossRefPubMedGoogle Scholar
  67. 67.
    Li HH, Ma F, Zeng X, et al. Comparison of fluorescence in situ hybridization and immunohistochemistry assessment for Her-2 status in breast cancer and its relationship to clinicopathological characteristics. Zhonghua Yi Xue Za Zhi. 2011;91(2):76–80.PubMedGoogle Scholar
  68. 68.
    Minot DM, Voss J, Rademacher S, et al. Image analysis of HER2 immunohistochemical staining. Reproducibility and concordance with fluorescence in situ hybridization of a laboratory-validated scoring technique. Am J Clin Pathol. 2012;137(2):270–6.CrossRefPubMedGoogle Scholar
  69. 69.
    Owens MA, Horten BC, Da-Silva MM. HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues. Clin Breast Cancer. 2004;5(1):63–9.CrossRefPubMedGoogle Scholar
  70. 70.
    Panjwani P, Epari S, Karpate A, 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;132:287–94.PubMedGoogle Scholar
  71. 71.
    Park YS, Hwang HS, Park HJ, et al. Comprehensive analysis of HER2 expression and gene amplification in gastric cancers using immunohistochemistry and in situ hybridization: which scoring system should we use? Hum Pathol. 2012;43(3):413–22.CrossRefPubMedGoogle Scholar
  72. 72.
    Pinhel I, Hills M, Drury S, et al. ER and HER2 expression are positively correlated in HER2 nonoverexpressing breast cancer. Breast Cancer Res Treat. 2012;14(2):R46.CrossRefGoogle Scholar
  73. 73.
    Ramalho S, Serra KP, Vassallo J, et al. HER2 expression in Brazilian patients with estrogen and progesterone receptor-negative breast carcinoma. Acta Histochem 2012 (in press).Google Scholar
  74. 74.
    Shigematsu H, Kadoya T, Kobayashi Y, et al. A case of HER-2-positive recurrent breast cancer showing a clinically complete response to trastuzumab-containing chemotherapy after primary treatment of triple-negative breast cancer. World J Surg Oncol. 2011;7(9):146.CrossRefGoogle Scholar
  75. 75.
    Tafe LJ, Janjigian YY, Zaidinski M, et al. Human epidermal growth factor receptor 2 testing in gastroesophageal cancer: correlation between immunohistochemistry and fluorescence in situ hybridization. Arch Pathol Lab Med. 2011;135(11):1460–5.CrossRefPubMedGoogle Scholar
  76. 76.
    Tanner M, Gancberg D, Di-Leo A, et al. Technical advance. Chromogenic in situ hybridization: a practical alternative for fluorescence in situ hybridization to detect HER-2/neu oncogene amplification in archival breast cancer samples. Am J Pathol. 2000;157(5):1467–72.PubMedCentralCrossRefPubMedGoogle Scholar
  77. 77.
    Thomson TA, Hayes MM, Spinelli JJ, et al. HER-2/neu in breast cancer: interobserver variability and performance of immunohistochemistry with 4 antibodies compared with fluorescent in situ hybridization. Mod Pathol. 2001;14(11):1079–86.CrossRefPubMedGoogle Scholar
  78. 78.
    Tvrdík D, Stanek L, Skálová H, et al. Comparison of the IHC, FISH, SISH and qPCR methods for the molecular diagnosis of breast cancer. Mol Med Report. 2012;6(2):439–43.Google Scholar
  79. 79.
    Varga Z, Tubbs RR, Wang Z, et al. Co-amplification of the HER2 gene and chromosome 17 centromere: a potential diagnostic pitfall in HER2 testing in breast cancer. Breast Cancer Res Treat. 2012;132(3):925–35.CrossRefPubMedGoogle Scholar
  80. 80.
    Wang S, Saboorian MH, Frenkel E, et al. Laboratory assessment of the status of Her-2/neu protein and oncogene in breast cancer specimens: comparison of immunohistochemistry assay with fluorescence in situ hybridisation assays. J Clin Pathol. 2000;53:374–81.PubMedCentralCrossRefPubMedGoogle Scholar
  81. 81.
    Yosepovich A, Avivi C, Bar J, et al. Breast cancer HER2 equivocal cases: is there an alternative to FISH testing? A pilot study using two different antibodies sequentially. Isr Med Assoc J. 2010;12(6):353–6.PubMedGoogle Scholar
  82. 82.
    Brown LD, Cai TT. Interval estimation for a binomial proportion. Stat Sci. 2001;16(2):101–33.Google Scholar
  83. 83.
    Lebeau A, Deimling D, Kaltz C, 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):354–63.PubMedGoogle Scholar
  84. 84.
    McCormick SR, Lillemoe TJ, Beneke J, et al. HER2 assessment by immunohistochemical analysis and fluorescence in situ hybridization. Am J Clin Pathol. 2002;117:935–43.CrossRefPubMedGoogle Scholar
  85. 85.
    Ellis CM, Dyson MJ, Stephenson TJ, et al. 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;58:710–4.PubMedCentralCrossRefPubMedGoogle Scholar
  86. 86.
    Ainsworth R, Bartlett JMS, Going JJ, et al. IHC for Her2 with CBE356 antibody is a more accurate predictor of Her2 gene amplification by FISH than HercepTestTM in breast carcinoma. J Clin Pathol. 2005;58:1086–90.PubMedCentralCrossRefPubMedGoogle Scholar
  87. 87.
    Dybdal N, Leiberman G, Anderson S, 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;93:3–11.CrossRefPubMedGoogle Scholar
  88. 88.
    Sapino A, Marchiò C, Senetta R, et al. Routine assessment of prognostic factors in breast cancer using a multicore tissue microarray procedure. Virchows Arch. 2006;449:288–96.CrossRefPubMedGoogle Scholar
  89. 89.
    Bergqvista J, Elmbergera G, Ohdb J, et al. Activated ERK1/2 and phosphorylated oestrogen receptor a are associated with improved breast cancer survival in women treated with tamoxifen. Eur J Cancer. 2006;42:1104–12.CrossRefGoogle Scholar
  90. 90.
    Powell WC, Hicks DG, Prescott N, et al. A new rabbit monoclonal antibody (4B5) for the immunohistochemical (IHC) determination of the HER2 status in breast cancer: comparison with CB11, fluorescence in situ hybridization (FISH), and interlaboratory reproducibility. Appl Immunohistochem Mol Morphol. 2007;15(1):94–102.CrossRefPubMedGoogle Scholar
  91. 91.
    Drev P, Grazio SF, Bracko M. Tissue microarrays for routine diagnostic assessment of HER2 status in breast carcinoma. Appl Immunohistochem Mol Morphol. 2008;16(2):179–84.CrossRefPubMedGoogle Scholar
  92. 92.
    Umemura S, Osamura RY, Akiyama F, Honma K, et al. What causes discrepancies in HER2 testing for breast cancer? Am J Clin Pathol. 2008;130:883–91.CrossRefPubMedGoogle Scholar
  93. 93.
    Gilbert JA, Goetz MP, Reynolds CA, et al. Molecular analysis of metaplastic breast carcinoma: high EGFR copy number via aneusomy. Mol Cancer Ther. 2008;7:944–51.PubMedCentralCrossRefPubMedGoogle Scholar
  94. 94.
    Vegt B, Bock GH, Bart JZNG, et al. Validation of the 4B5 rabbit monoclonal antibody in determining Her2/neu status in breast cancer. Mod Pathol. 2009;22:879–86.CrossRefPubMedGoogle Scholar
  95. 95.
    Rhodes A, Sarson J, Assam E, et al. The reliability of rabbit monoclonal antibodies in the immunohistochemical assessment of estrogen receptors, progesterone receptors, and HER2 in human breast carcinomas. Am J Clin Pathol. 2010;134:621–32.CrossRefPubMedGoogle Scholar
  96. 96.
    Grimm EE, Schmidt RA, Swanson PE, et al. Achieving 95% cross-methodological concordance in HER2 testing. Am J Clin Pathol. 2010;134:284–92.CrossRefPubMedGoogle Scholar
  97. 97.
    Dowsett M, Cooke T, Ellis I, et al. Assessment of HER2 status in breast cancer: why, when and how? Eur J Cancer. 2000;36:170–6.CrossRefPubMedGoogle Scholar
  98. 98.
    Horiguchi S, Hishima T, Hayashi Y, et al. HER-2/neu cytoplasmic staining is correlated with neuroendocrine differentiation in breast carcinoma. J Med Dent Sci. 2010;57:155–63.PubMedGoogle Scholar
  99. 99.
    Vogel UF. Confirmation of a low HER2 positivity rate of breast carcinomas-limitations of immunohistochemistry and in situ hybridization. Diagn Pathol. 2010;5:50–8.PubMedCentralPubMedGoogle Scholar

Copyright information

© The Japanese Breast Cancer Society 2014

Authors and Affiliations

  • Fatemeh Bahreini
    • 1
  • Ali Reza Soltanian
    • 2
  • Parvin Mehdipour
    • 1
    Email author
  1. 1.Department of Medical Genetics, School of MedicineTehran University of Medical SciencesTehranIran
  2. 2.Department of Biostatistics and Epidemiology, Modeling of Noncommunicable Diseases Research Center, School of Public HealthHamadan University of Medical SciencesHamadanIran

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