The Discordance Between HER-2/NEU Expression Assessed by Immunohistochemistry (IHC) and Fluorescence in Situ Hybridization (FISH): Is It Important to Detect?
Year 2014,
Volume: 39 Issue: 1, 53 - 60, 22.07.2014
Purpose: Assessment of HER-2 has become of great importance following the advent of HER-2 antibody treatment. Use of trastuzumab therapy depends on the assessment of HER-2 via standard immunohistochemistry (IHC) assays for protein overexpression or via fluorescence in situ hybridization (FISH) for gene amplification. The aim of this study was to determine the rate of discordance between FISH and IHC in our hospital. The rate of discordance varies from hospital to hospital, and due to certain staff, technical, and biological reasons, IHC and FISH may not be concordant in every patient. It is important to determine the rate of discordance between these 2 methods and attempt to lower it. In addition to the rate of discordance, we also investigated the reasons for the discordance and what affect it has on the progression of the disease and treatment. Material and Methods: A total of 79 patients with breast cancer were assessed for HER-2 protein expression via IHC and HER-2 gene amplification via FISH. Results: Among these 79 patients, 47 (59.5%) were FISH (-) and 32 (40.5%) were FISH (+), whereas FISH was negative in 8 (10.4%) patients that were HER-2 (3+) and FISH was positive in 9 (11.4%) patients that were HER-2 (1+). The discordance rate was 21.5%. Conclusion: The clinical implication of this discordance rate and it's affect on the choice of appropriate therapy are of critical importance. As such, it would be beneficial for each hospital to determine its own discordance rate.
Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer correlation of relapse and survival with amplification of the HER2/neu oncogene. Science. 1987;235:177-82.
Wollf AC, Hammond EH, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Clin Oncol. 2007;25:118-45.
Harris L, Fritsche H, Mennel R, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25:5287.
National Comprehensive Cancer Network (NCCN) Guidelines available online at www.nccn.org/professionals/physician_gls/f_guidelin es.asp (Accessed May 12, 2009).
Sturgeon CM, Hoffman BR, Chan DW, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in clinical practice: quality requirements. Clin Chem 2008;54: e1.
Layfield LJ, Willmore-Payne C, Isom G, Holden JA. Monoplex LightCycler polymerase chain reaction quantitation of the HER2 gene for quality assurance of HER2/neu testing by immunohistochemistry and fluorescence in situ hybridization. Appl Immunohistochem Mol Morphol. 2008;16:562-7.
Bast RC Jr, Ravdin P, Hayes DF, et al. 2000 update of recommendations for the use of tumor markers in breast and colorectal cancer clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2001;19:1865-78.
Pauletti G, Dandekar S, Rong H, et al. Assessment of methods for tissue-based detection of the Her2/neu alteration in human breast cancer: a direct comparison of fluorescence in situ hybridization and immunohistochemistry. Clin Oncol. 2000;18:3651
Carter P, Presta L, Gorman CM, et al. Humanization of an anti-p185HER2 antibody for human cancer therapy . Proc Natl Acad Sci USA. 1992;89:4285-9.
Vogel CL, Cobleigh MA, Tripathy D, 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;20:719-26.
Yamauchi H, Stearns V, Hayes DF. When is a tumor ready for prime time? A case study o cerb B-2 as a predictive factor in breast cancer. J Clin Oncol. 2001;19:2334-56.
Konecny G, Pauletti G, Pegram M, et al. Quantative association between Her2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer. J Natl Cancer Inst. 2003;95:142-53.
Paik S, Hazan R, Fisher ER, et al. Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein overexpression in primary breast cancer. J Clin Oncol. 1990;8:103.
Van de Vijver MJ, Mooi WJ, Wisman P, et al. Immunohistochemical detection of the neu protein in tissue sections of human breast tumors with amplified neu DNA. Oncogene. 1988;2:175.
Gilcrease MZ, Woodward WA, Nicolas MM, et al. Even Low-level HER2 Expression May be Associated With Worse Outcome in Node-positive Breast Cancer. Am J Surg Pathol. 2009;33:759.
Taucher S, Rudas M, Mader RM, et al. Do we need HER-2/neu testing for all patients with primary breast carcinoma? Cancer. 2003;98:2547.
Laudadio J, Quigley DI, Tubbs R, Wollf DJ. HER2 testing: a review of detection methodologies and their clinic performance. Expert Rev Mol Diagn. 2007;7:53
Ross JS, Fletcher JA, Linette GP, et al. The Her2/neu gene and protein in breast cancer 2003: biomarker and target of therapy. Oncologist. 2003;8:307-25.
Zhou BP, Hung MC. Dysregulation of cellular signaling by HER2/neu in breast cancer. Semin Oncol. 2003;30:38-48.
Menard S, Casalini P, Campiglio M, Pupa SM, Tagliabue E. Role of Her2/neu in tumor progression and therapy. Cell Mol Life Sci. 2004;61: 2965-78.
Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2 . N Eng J Med. 2001;344:783
Marty M, Cognetti F, Maraninchi D, et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor2 positive metastatic breast cancer administered as first line treatment: the M77001study group. J Clin Oncol. 2005;23:4265-74.
Piccart –Gebhart MI, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Eng J Med. 2005;353:1659-72.
Smith I, Roctor M, Gelber RD, et al. 2-year follow up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomized controlled trial. Lancet. 2007;369:36-9.
Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2positive breast cancer. N Eng J Med. 2005;353:1673
Slamon D, EiermannW, Robert N, et al. Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (ACT) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (ACTH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2 positive early breast cancer patients BCIRG 006study. Breast Cancer Res Treat 2005;94:55.
Joensuu H, Kellokumpu-Lehtinen PL, Bono P, et al. Adjuvant docetaxel or vinorelbin with or without trastuzumab for breast cancer. N Eng J Med. 2006;354:809-20.
Ellis IO, Bartlett J, Dowsett M, et al. Best Practice No 176: updated recommendations for HER2 testing in UK. J Clin Pathol. 2004;57:233-7.
Paik S, Bryant J, Tan Chiu E, et al. Real-world performance of Her2 testing-National Surgical Adjuvan Breast and Bowel Project experience. J Natl Cancer Inst. 2002;94:855-7.
O’Malley EP, Thomson T, Julian J, et al. HER2 testing in a population-based study of patients with metastatic breast cancer treated with trastuzumab. Arch Pathol Lab Med. 2008;132:61-5.
Zuo T, Wang L, Morrison C, et al. FOXP3 is an Xlinked breast cancer suppressor gene and an important repressor of the HER-2/ErbB2 oncogene. Cell. 2007;129:1275-86.
Acs G, Wang L, Raghunath PN, Salscheider MA, Zhang PJ. Role of different immunostaining patterns in HercepTest interpretation and criteria for gene amplification as determined by fluorescence in situ hybridization. Appl Immunohistochem Mol Morphol. 2003;11:222-9.
Leong AS, Formby M, Haffajee Z, Clarke M, Morey A. Refinement of immunohistologic parameters for Her2/neu scoring validation by FISH and CISH. Appl Immunohistochem Mol Morphol.2006;14:384-9.
Tandon AK, Clark GM, Chamness GC, et al. HER2/neu oncogene protein and prognosis in breast cancer. J Clin Oncol 1989;7:1120
Gusterson BA, Gelber RD, Goldhirsch A, et al. Prognostic importance of c-erbB-2 expression in breast cancer .International(Ludwig) Breast Cancer Study Group. J Clin Oncol. 1992;10:1049.
Kroger N, Milde-Langosch K, Riethdorf S, et al. Prognostic and predictive effects of immunohistochemical factors in high-risk primary breast cancer patients. Clin Cancer Res. 2006;12:159.
Chia S, Norris B, Speers C, et al. Human epidermal growth factor receptor 2 overexpression as a prognostic factor in a large tissue microarray series of node-negative breast cancers. J Clin Oncol. 2008;26:5697.
Goldhirsch A, Wood WC, Gelber RD, et al. Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer. Ann Oncol. 2007;18:1133.
Barlett JM. Pharmacodiagnostic testing in breast cancer: focus on HER2 and trastuzumab therapy. Am J Pharmacogenomics. 2005;5:303-15.
Yazışma Adresi / Address for Correspondence: Dr. Berna Bozkurt Duman Çukurova University Faculty of Medicine Department of Medical Oncology 01330, Sarıçam/ADANA
Email: berboz@hotmail.com geliş tarihi/received :12.08.2013 kabul tarihi/accepted:16.09.2013
HER-2/NEU Ekspresyonun Saptanmasinda İmmunohistokimyasal ve Fish Yöntemi Arasında Diskordansin Belirlenmesi Önemli midir?
Year 2014,
Volume: 39 Issue: 1, 53 - 60, 22.07.2014
Amaç: HER-2"nin değerlendirilmesi, HER-2 antikor tedavisinin takibinde büyük öneme sahiptir. Transtuzumab tedavisinde HER-2"nin değerlendirilmesi protein aşırı üretiminin standart immünohistokimyasal yöntemler ile veya gen amplifikasyonunun FISH yöntemi ile belirlenmesine bağlıdır. Bu çalışmanın amacı hastanemizde kullanılan bu iki yöntem arasındaki diskordans oranını incelemektir. Diskordans oranı hastaneler arasında farklılık göstermektedir, bu farklılık çalışanlara, teknik nedenlere ve biyolojik nedenlere bağlı olabilmektedir. Dolayısıyla bu iki metod arasındaki diskordans oranını belirlemek ve bu oranı minimize önemlidir. Bunlara ek olarak, diskordansın sebeplerini, hastalığın ve tedavinin progresyonu üzerine nasıl etki ettiğini araştırdık. Materyal ve Metod: Meme kanseri tanısı alan toplam 79 hastada HER-2 protein ekspresyonu immunohistokimyasal, HER-2 gen amplifikasyonu ise FISH yöntemleriyle incelendi. Bulgular: İncelenen 79 hastadan 47 sinde (%59.5) FISH (-) 32 sinde (%40.5) FISH (+), öte yandan FISH negatif olan 8 (%10.4) hasta için HER-2 (3+) ve FISH pozitif 9 hasta (%11.4) içinde HER-2 (1+) bulundu. Diskordans oranı %21.5 tir. Sonuç: Diskordans oranının klinik implikasyonu uygun tedavi prosedürünü seçmek için önemlidir, bu yaklaşım hastanelerin kendi diskordans oranlarını belirlemeleri için faydalı olabilir.
Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer correlation of relapse and survival with amplification of the HER2/neu oncogene. Science. 1987;235:177-82.
Wollf AC, Hammond EH, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Clin Oncol. 2007;25:118-45.
Harris L, Fritsche H, Mennel R, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25:5287.
National Comprehensive Cancer Network (NCCN) Guidelines available online at www.nccn.org/professionals/physician_gls/f_guidelin es.asp (Accessed May 12, 2009).
Sturgeon CM, Hoffman BR, Chan DW, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in clinical practice: quality requirements. Clin Chem 2008;54: e1.
Layfield LJ, Willmore-Payne C, Isom G, Holden JA. Monoplex LightCycler polymerase chain reaction quantitation of the HER2 gene for quality assurance of HER2/neu testing by immunohistochemistry and fluorescence in situ hybridization. Appl Immunohistochem Mol Morphol. 2008;16:562-7.
Bast RC Jr, Ravdin P, Hayes DF, et al. 2000 update of recommendations for the use of tumor markers in breast and colorectal cancer clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2001;19:1865-78.
Pauletti G, Dandekar S, Rong H, et al. Assessment of methods for tissue-based detection of the Her2/neu alteration in human breast cancer: a direct comparison of fluorescence in situ hybridization and immunohistochemistry. Clin Oncol. 2000;18:3651
Carter P, Presta L, Gorman CM, et al. Humanization of an anti-p185HER2 antibody for human cancer therapy . Proc Natl Acad Sci USA. 1992;89:4285-9.
Vogel CL, Cobleigh MA, Tripathy D, 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;20:719-26.
Yamauchi H, Stearns V, Hayes DF. When is a tumor ready for prime time? A case study o cerb B-2 as a predictive factor in breast cancer. J Clin Oncol. 2001;19:2334-56.
Konecny G, Pauletti G, Pegram M, et al. Quantative association between Her2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer. J Natl Cancer Inst. 2003;95:142-53.
Paik S, Hazan R, Fisher ER, et al. Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein overexpression in primary breast cancer. J Clin Oncol. 1990;8:103.
Van de Vijver MJ, Mooi WJ, Wisman P, et al. Immunohistochemical detection of the neu protein in tissue sections of human breast tumors with amplified neu DNA. Oncogene. 1988;2:175.
Gilcrease MZ, Woodward WA, Nicolas MM, et al. Even Low-level HER2 Expression May be Associated With Worse Outcome in Node-positive Breast Cancer. Am J Surg Pathol. 2009;33:759.
Taucher S, Rudas M, Mader RM, et al. Do we need HER-2/neu testing for all patients with primary breast carcinoma? Cancer. 2003;98:2547.
Laudadio J, Quigley DI, Tubbs R, Wollf DJ. HER2 testing: a review of detection methodologies and their clinic performance. Expert Rev Mol Diagn. 2007;7:53
Ross JS, Fletcher JA, Linette GP, et al. The Her2/neu gene and protein in breast cancer 2003: biomarker and target of therapy. Oncologist. 2003;8:307-25.
Zhou BP, Hung MC. Dysregulation of cellular signaling by HER2/neu in breast cancer. Semin Oncol. 2003;30:38-48.
Menard S, Casalini P, Campiglio M, Pupa SM, Tagliabue E. Role of Her2/neu in tumor progression and therapy. Cell Mol Life Sci. 2004;61: 2965-78.
Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2 . N Eng J Med. 2001;344:783
Marty M, Cognetti F, Maraninchi D, et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor2 positive metastatic breast cancer administered as first line treatment: the M77001study group. J Clin Oncol. 2005;23:4265-74.
Piccart –Gebhart MI, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Eng J Med. 2005;353:1659-72.
Smith I, Roctor M, Gelber RD, et al. 2-year follow up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomized controlled trial. Lancet. 2007;369:36-9.
Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2positive breast cancer. N Eng J Med. 2005;353:1673
Slamon D, EiermannW, Robert N, et al. Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (ACT) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (ACTH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2 positive early breast cancer patients BCIRG 006study. Breast Cancer Res Treat 2005;94:55.
Joensuu H, Kellokumpu-Lehtinen PL, Bono P, et al. Adjuvant docetaxel or vinorelbin with or without trastuzumab for breast cancer. N Eng J Med. 2006;354:809-20.
Ellis IO, Bartlett J, Dowsett M, et al. Best Practice No 176: updated recommendations for HER2 testing in UK. J Clin Pathol. 2004;57:233-7.
Paik S, Bryant J, Tan Chiu E, et al. Real-world performance of Her2 testing-National Surgical Adjuvan Breast and Bowel Project experience. J Natl Cancer Inst. 2002;94:855-7.
O’Malley EP, Thomson T, Julian J, et al. HER2 testing in a population-based study of patients with metastatic breast cancer treated with trastuzumab. Arch Pathol Lab Med. 2008;132:61-5.
Zuo T, Wang L, Morrison C, et al. FOXP3 is an Xlinked breast cancer suppressor gene and an important repressor of the HER-2/ErbB2 oncogene. Cell. 2007;129:1275-86.
Acs G, Wang L, Raghunath PN, Salscheider MA, Zhang PJ. Role of different immunostaining patterns in HercepTest interpretation and criteria for gene amplification as determined by fluorescence in situ hybridization. Appl Immunohistochem Mol Morphol. 2003;11:222-9.
Leong AS, Formby M, Haffajee Z, Clarke M, Morey A. Refinement of immunohistologic parameters for Her2/neu scoring validation by FISH and CISH. Appl Immunohistochem Mol Morphol.2006;14:384-9.
Tandon AK, Clark GM, Chamness GC, et al. HER2/neu oncogene protein and prognosis in breast cancer. J Clin Oncol 1989;7:1120
Gusterson BA, Gelber RD, Goldhirsch A, et al. Prognostic importance of c-erbB-2 expression in breast cancer .International(Ludwig) Breast Cancer Study Group. J Clin Oncol. 1992;10:1049.
Kroger N, Milde-Langosch K, Riethdorf S, et al. Prognostic and predictive effects of immunohistochemical factors in high-risk primary breast cancer patients. Clin Cancer Res. 2006;12:159.
Chia S, Norris B, Speers C, et al. Human epidermal growth factor receptor 2 overexpression as a prognostic factor in a large tissue microarray series of node-negative breast cancers. J Clin Oncol. 2008;26:5697.
Goldhirsch A, Wood WC, Gelber RD, et al. Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer. Ann Oncol. 2007;18:1133.
Barlett JM. Pharmacodiagnostic testing in breast cancer: focus on HER2 and trastuzumab therapy. Am J Pharmacogenomics. 2005;5:303-15.
Yazışma Adresi / Address for Correspondence: Dr. Berna Bozkurt Duman Çukurova University Faculty of Medicine Department of Medical Oncology 01330, Sarıçam/ADANA
Email: berboz@hotmail.com geliş tarihi/received :12.08.2013 kabul tarihi/accepted:16.09.2013
Duman, Berna Bozkurt et al. “HER-2/NEU Ekspresyonun Saptanmasinda İmmunohistokimyasal Ve Fish Yöntemi Arasında Diskordansin Belirlenmesi Önemli Midir?”. Cukurova Medical Journal, vol. 39, no. 1, 2014, pp. 53-60, doi:10.17826/cutf.65640.