HER2 Testing: Insights From Pathologists’ Perspective on Technically Challenging HER2 FISH Cases

Objective: College of American Pathologists and the American Society of Clinical Oncology guidelines provide straightforward criteria for HER2 interpretation in breast carcinomas; however, a subset of cases present unusual diagnostic dilemmas. Materials and Methods: Ten challenging HER2 fluorescence in situ hybridization (FISH) cases were selected for analysis. The study included a variety of problematic cases such as those with discordant immunohistochemistry (IHC) and FISH results, cases with high intratumoral variability in HER2 copy number, a case with a highly amplified clone in 5% to 10% of the tumor sample, and a case with tumor cells containing tightly clumped HER2 signals. Six high volume HER2 FISH laboratories performed and interpreted HER2 FISH (adding HER2 IHC if necessary). Interpretation strategies were discussed. Results: There was 100% concordance between laboratories in 4/10 cases. Tumors with increased intratumoral variability (tumors with high variability in HER2 copy number per cell but which otherwise do not fulfill College of American Pathologists and the American Society of Clinical Oncology criteria for heterogeneity) exhibited 100% concordance in 3/4 cases, but 1 case had only 50% agreement. Low positive HER2 cases (group 1 cases with
Source: Applied Immunohistochemistry and Molecular Morphology - Category: Chemistry Tags: Research Article Source Type: research