The New Equivocal: Changes to HER2 FISH Results When Applying the 2013 ASCO/CAP Guidelines.

OBJECTIVES: Human epidermal growth factor receptor 2 (HER2, ERBB2) testing is an important prognostic/predictive marker in breast cancer management, especially in selecting HER2-targeted treatment. American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines address HER2 status and were recently revised in 2013, replacing the 2007 version. For in situ hybridization interpretation, 2013 guidelines return to the prior threshold of a HER2/CEP17 ratio of 2.0 or greater for positive and eliminate 1.8 to 2.2 as the equivocal range. Also, the HER2 signal/nucleus ratio is accounted for, with 6.0 or greater for positive and 4.0 to less than 6.0 for equivocal, even in cases with a HER2/CEP17 ratio less than 2.0.
METHODS: With institutional review board approval, we reviewed our 2006 to 2012 HER2 fluorescence in situ hybridization (FISH) results and classified them according to both the 2007 and 2013 guidelines as negative, positive, or equivocal.
RESULTS: Of 717 HER2 FISH results, 55 (7.7%) changed category when reassessed by 2013 guidelines. Nineteen of 25 results in the 2007 equivocal category were reassigned as positive (n = 13) or negative (n = 6). Thirty-five previously negative cases became equivocal in the 2013 scheme, 12 of these with 1+ immunohistochemistry. The positive category increased from 71 to 85.
CONCLUSIONS: The 2013 ASCO/CAP guidelines increased the number of HER2 FISH positive and equivocal results. The equivocal group is substantially different, posing a dilemma for clinical management. Copyright© by the American Society for Clinical Pathology.