Analysis of racial differences in HER2 status and molecular subtype in grade 3 endometroid endometrial carcinoma

To characterize stage I-III Grade 3 endometroid endometrial cancer (Gr3 EEC) by molecular subtype and human epithelial growth factor receptor 2 (HER2) status and explore differences in characteristics by race.

We identified patients with a diagnosis of stage I-III Gr3 EEC from a single-institution health system cancer registry and pathologically confirmed the diagnosis. Review of the electronic health record was performed as needed to confirm patient characteristics. Next-generation sequencing (NGS) and immunohistochemical staining (IHC) for HER2 was performed on all primary tumors.

Thirty-four primary cases remained classified as stage I-III Gr3 EEC after pathologic review and exclusion of cases lacking in-house primary tumor for re-review. Fifteen were categorized as microsatellite unstable (MSI; 44 %), 10 as copy number high (CNH; 29 %), six as polymerase E mutant (POLEmut; 17.6 %) and three as copy number low (CNL; 8.8 %). Thirteen patients were Black, 18 were White, and 3 had a race of "other and/or unknown". HER2 status by IHC in the primary tumor was 0 (n = 7; 20.5 %), 1+ (n = 11; 32 %), 2+ (n = 14; 41 %), 3+ (n = 1; 3 %). There was no difference in the distribution of TCGA subtype or HER2 status by race.

In stage I-III stage Gr3 EEC HER2 positivity (3 + ) was uncommon, but expression at the 2 + level was frequent, and did not differ by race. In this limited sample, there were no differences in distribution of TCGA subtype amongst patients with grade 3 EEC. Other causes should be explored to explain reported differences in outcomes in EEC by race.