HER2 testing by immunohistochemistry in breast cancer: A multicenter proficiency ring study

Area of Science:

• Oncology
• Pathology
• Molecular Diagnostics

Background:

• Human epidermal growth factor receptor 2 (HER2) overexpression in breast cancer is linked to aggressive disease and response to targeted therapies.
• Accurate HER2 testing is crucial for effective patient management.
• Routine HER2 immunohistochemistry (IHC) testing exhibits variability between laboratories.

Purpose of the Study:

• To evaluate inter-laboratory variability in HER2 IHC testing.
• To assess concordance rates through a slide-exchange program involving five reference laboratories.

Main Methods:

• Twenty breast carcinoma cases with known HER2 status were used.
• Participating labs performed HER2 IHC on provided slides.
• Results were interpreted centrally, with discordant slides re-evaluated.

Main Results:

• Concordance was high for clearly positive (6/6) and negative (6/6) cases confirmed by in-situ hybridization (ISH).
• Discordant results occurred in 6 equivocal, 1 negative, and 1 positive case, yielding a 50-88.3% concordance rate.
• Tumor heterogeneity was noted in a discordant negative case; good inter-observer agreement (k=0.713-1.0) was achieved.

Conclusions:

• Standardization of HER2 testing protocols is essential for improving inter-laboratory concordance.
• Equivocal cases and intra-tumoral heterogeneity present challenges in accurate HER2 scoring.
• Continuous quality assessment is vital for reliable HER2 IHC results.