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Molecular Diagnostics in Cancer Patients pp 237–268Cite as

Molecular Pathway and Fluorescence In Situ Hybridization Testing of ERBB2 (HER2) Gene Amplification in Invasive Ductal Carcinoma of Breast

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Abstract

Standard screening of breast tumors involves morphologic, immunohistochemistry (IHC), and Fluorescence in Situ Hybridization (FISH) analyses to assess pathogenicity and to identify possible treatment strategies. Among breast cancer types, invasive ductal carcinoma (IDC), in particular, exhibits amplification of the HER2 (ERBB2) gene that can be detected by FISH as defined by the current American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP, 2013, 2018) scoring guidelines. One criterion for amplification of the HER2 gene is based on the ratio of HER2 gene signals to centromere 17 signals obtained from microscopic analysis of 20 cells by FISH. A second criterion requires an average of more than 6 copies of HER2 signals per cell out of 20 cells screened by FISH. If either of these criteria is met, then individualized therapy with adjuvant chemotherapy and the HER2-targeted drug Trastuzumab (Herceptin®) is indicated, which remarkably improves prognosis by decreasing local recurrence and metastasis. If HER2 is not amplified in IDC of breast, further testing is performed and alternative treatments are considered which may have less favorable prognoses. Genetic heterogeneity (GH) is when IDC of breast has between 5 and 50% of cells that are positive for HER2 amplification by FISH. Such cases fall short in meeting the amplified status criteria currently mandated by ASCO/CAP. Based on our, and data from literature review, an update to the most recent ASCO/CAP guideline (issued in June 2018) criteria for positive amplification to include HER2 GH+ cases with greater than 25% HER2 amplification would extend the beneficial HER2-targeted therapy that is regulated by ASCO and the FDA to an additional 8% of patients .

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Authors and Affiliations

  1. Department of Pathology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY, USA

    Tomasz Jodlowski

  2. Clinical Cytogenetics and Genomics, Department of Pathology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY, USA

    K. H. Ramesh

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  1. Tomasz Jodlowski
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Correspondence to K. H. Ramesh .

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  1. Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India

    Kamla Kant Shukla

  2. Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India

    Praveen Sharma

  3. Department of Surgical Oncology, All India Institute of Medical Sciences, Jodhpur, India

    Sanjeev Misra

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Jodlowski, T., Ramesh, K.H. (2019). Molecular Pathway and Fluorescence In Situ Hybridization Testing of ERBB2 (HER2) Gene Amplification in Invasive Ductal Carcinoma of Breast. In: Shukla, K., Sharma, P., Misra, S. (eds) Molecular Diagnostics in Cancer Patients. Springer, Singapore. https://doi.org/10.1007/978-981-13-5877-7_15

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