HER2 (ERBB2) overexpression in breast cancer is used to guide trastuzumab therapy. Per ASCO/CAP 2018 guidelines, HER2 IHC result of 2+ (equivocal) mandates which confirmatory test, and what defines HER2 positivity by that test?
- A FISH or ISH; HER2/CEP17 ratio ≥2.0 OR average HER2 copy number ≥6 signals/cell ✓
- B ER/PR immunohistochemistry; >1% nuclear staining = positive
- C Ki-67 labeling index; >20% = high proliferation indicating HER2 amplification
- D PCR for ERBB2 mRNA; >2-fold upregulation = positive
Correct answer: A. FISH or ISH; HER2/CEP17 ratio ≥2.0 OR average HER2 copy number ≥6 signals/cell
Explanation
Per ASCO/CAP 2018 HER2 testing guidelines, IHC 2+ (equivocal, incomplete membrane staining >10% tumor cells) requires reflex FISH/ISH testing. HER2 positivity by FISH is defined as HER2/CEP17 ratio ≥2.0 AND/OR average HER2 copy number ≥6 signals/cell. The 2018 update created four dual-probe ISH groups with specific combinations of ratio and copy number requiring additional IHC correlation. IHC 3+ (complete intense membrane staining >10% of cells) is directly positive without requiring FISH confirmation.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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