Her2/neu Status Determination in Breast Cancer: A Single Institutional Experience Using a Dual-Testing Approach With Immunohistochemistry and Fluorescence In Situ Hybridization.
OBJECTIVE
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.
From the Department of Pathology, University of California San Diego, La Jolla.
James P
JP
Solomon
From the Department of Pathology, University of California San Diego, La Jolla.
Marie
M
Dell'Aquila
From the Department of Pathology, University of California San Diego, La Jolla.
Oluwole
O
Fadare
From the Department of Pathology, University of California San Diego, La Jolla.
Farnaz
F
Hasteh
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
Ancillary testing; Breast carcinoma; ERBB2; Fluorescence in situ hybridization; Her2/neu