Interobserver and Interantibody Reproducibility of HER2 Immunohistochemical Scoring in an Enriched HER2-Low–Expressing Breast Cancer Cohort. Issue 5 (28th February 2023)

• Record Type: Journal Article
• Authors: Karakas, Cansu; Tyburski, Haley; Turner, Bradley M; Wang, Xi; Schiffhauer, Linda M; Katerji, Hani; Hicks, David G; Zhang, Huina
• Is Part Of: American journal of clinical pathology. Volume 159:Issue 5(2023)
• Page Start: 484
• Page End: 491
• Publication Date: 2023-02-28
• Subjects: HER2 -- HER2-low -- Breast cancer -- HercepTest -- 4B5 -- Reproducibility; Diagnosis, Laboratory -- Periodicals; Pathology -- Periodicals; 616.07
• DOI: 10.1093/ajcp/aqac184
• Languages: English
• ISSNs: 0002-9173

Abstract

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.