Interobserver and Interantibody Reproducibility of HER2 Immunohistochemical Scoring in an Enriched HER2-Low–Expressing Breast Cancer Cohort

• Published in: American journal of clinical pathology Vol. 159; no. 5; pp. 484 - 491
• Main Authors: Karakas, Cansu, Tyburski, Haley, Turner, Bradley M, Wang, Xi, Schiffhauer, Linda M, Katerji, Hani, Hicks, David G, Zhang, Huina
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 02.05.2023
• Subjects: Analysis; Antibodies; Biomarkers, Tumor - metabolism; Breast cancer; Breast Neoplasms - metabolism; ErbB-2 protein; Female; Humans; Immunohistochemistry; Immunohistochemistry - methods; Receptor, ErbB-2 - metabolism; Reproducibility; Reproducibility of Results; Viral antibodies; HER2-low; Breast cancer; HercepTest; HER2; Reproducibility; 4B5
• ISSN: 0002-9173; 1943-7722
• DOI: 10.1093/ajcp/aqac184

Abstract Objectives We assessed the interobserver and interantibody reproducibility of HER2 immunohistochemical scoring in an enriched HER2-low–expressing breast cancer cohort. Methods A total of 114 breast cancer specimens were stained by HercepTest (Agilent Dako) and PATHWAY anti-HER2 (4B5) (Ventana) antibody assays and scored by 6 breast pathologists independently using current HER2 guidelines. Level of agreement was evaluated by Cohen κ analysis. Results Although the interobserver agreement rate for both antibodies achieved substantial agreement, the average rate of agreement for HercepTest was significantly higher than that for the 4B5 clone (74.3% vs 65.1%; P = .002). The overall interantibody agreement rate between the 2 antibodies was 57.8%. Complete interobserver concordance was achieved in 44.7% of cases by HercepTest and 45.6% of cases by 4B5. Absolute agreement rates increased from HER2 0-1+ cases (78.1% by HercepTest and 72.2% by 4B5; moderate agreement) to 2-3+ cases (91.9% by HercepTest and 86.3% by 4B5; almost perfect agreement). Conclusions Our results demonstrated notable interobserver and interantibody variation on evaluating HER2 immunohistochemistry, especially in cases with scores of 0-1+, although the performance was much more improved among breast-specialized pathologists with the awareness of HER2-low concept. More accurate and reproducible methods are needed for selecting patients who may benefit from the newly approved HER2-targeting agent on HER2-low breast cancers.