172 Optimizing Human Epidermal Growth Factor Receptor 2 (HER2) Testing in Endometrial Cancers: A Comparative Analysis of Immunohistochemistry (IHC), Chromogenic In Situ Hybridization (CISH) and Next Generation Sequencing (NGS)

Introduction/Objective HER2 is a is a well-known prognostic and therapeutic biomarker in breast cancer with a high concordance rate (>90%) between IHC and CISH. Concordance in uterine cancers is less established. Since NGS has become standard for uterine cancers, we seek to determine if NGS alone would capture HER2 abnormalities. Methods/Case Report The laboratory information system was searched for endometrial cancers with NGS testing between August 2023-January 2025. Parameters collected included tumor histologic type, HER2 IHC and CISH results, ERBB2 copy number, tumor mutational burden, and tumor cellularity. Concordance rates between NGS and IHC and CISH were calculated. Results NA Conclusion We identified 120 gynecologic cancer cases with NGS testing; 10 had concurrent IHC and CISH and 35 had only concurrent IHC. Concordance rates for NGS with IHC and CISH were 100% and 88.9% (excluding equivocal/indeterminate cases), respectively. The single discordant case was ERBB2 copy number high (7.2) by NGS but CISH negative (IHC equivocal). For this case, NGS and CISH were performed on different blocks. Tumor cellularity was 70%. This study was limited by a low case number, particularly low ERBB2 positive cases. The overall high concordance rate between NGS and IHC and CISH suggests the possibility of streamlining testing algorithms.