Objectives: According to current guidelines, either immunohistochemistry (IHC) or in situ hybridization (ISH) can be used to determine human epidermal growth factor receptor 2 (Her2/neu) status in breast carcinoma. While the guidelines explicitly delineate result interpretation, there is no consensus on the most appropriate testing algorithm.
Methods: The Her2/neu statuses of 369 consecutive cases of invasive breast cancer (from 351 patients) were assessed in a dual-testing algorithm that uses both IHC and fluorescence ISH (FISH). FISH was performed using dual-color HER2/ chromosome enumeration probe 17 ( CEP17 ) probes, and if equivocal results were obtained, reflex testing using HER2/lissencephaly gene 1 ( LIS1 ) probes was used. Results from both modalities were scored and reported using American Society of Clinical Oncology/College of American Pathologists 2013 criteria.
Results: Sixty-one (16.5%) of the 369 tumors were found to be Her2/neu positive by at least one modality. The overall concordance between IHC and FISH results was 97.6%. Six of the 369 tumors were reclassified as Her2/neu positive after a negative IHC result. FISH was also able to identify significantly more Her2/neu-positive cases than IHC.
Conclusions: The commonly used reflex strategy based on IHC results may deny potentially beneficial targeted therapy for a small cohort of patients, which should be considered as testing guidelines are formulated and the cost-benefit analyses of various testing algorithms are assessed.
Keywords: Ancillary testing; Breast carcinoma; ERBB2; Fluorescence in situ hybridization; Her2/neu.
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