Changes in HER2 Amplification Status for Breast Cancer Patients After Immunohistochemistry Directed In Situ...

Area of Science:

• Oncology
• Molecular Diagnostics
• Pathology

Background:

• The 2018 ASCO/CAP guidelines introduced immunohistochemistry (IHC)-directed in situ hybridization (ISH) recount for equivocal HER2 results in breast cancer.
• This addition aimed to resolve ambiguous cases but introduced complexity into the diagnostic workflow.

Purpose of the Study:

• To evaluate the impact of the 2+ IHC-directed ISH recount on HER2 testing results for equivocal cases.
• To analyze changes in HER2 amplification status and associated metrics following the guideline implementation.

Main Methods:

• Retrospective review of equivocal ISH cases (groups 2, 3, and 4) tested since the 2018 guidelines.
• Analysis of changes in HER2 group number and amplification status after 2+ IHC-directed ISH recount.
• Comparison of HER2/CEP17 ratio and HER2 signal number per cell before and after IHC-guided recount.

Main Results:

• HER2 group number and amplification status frequently changed post-IHC-directed ISH recount.
• Changes were driven by significant alterations in HER2/CEP17 ratio and average HER2 signal number per cell.
• Equivocal samples ultimately classified as HER2-amplified showed higher initial ISH counts closer to the amplification threshold.

Conclusions:

• The IHC-guided ISH recount significantly impacts HER2 testing outcomes for a subset of breast cancer patients.
• This reassessment can lead to a shift in therapeutic options based on revised HER2 amplification status.
• The study highlights the clinical significance of resolving equivocal HER2 ISH results.