Assessment of HER2 in Gastric-Type Endocervical Adenocarcinoma and its Prognostic Significance

As the most common type of human papillomavirus-independent endocervical adenocarcinomas (ECAs), gastric-type endocervical adenocarcinomas (GEAs) account for approximately 10% of all ECAs. Although anti-HER2 therapy has been proven effective in many cancers, it has not been used in ECAs, including GEAs, which is at least partly due to the lack of a well-defined guideline. Limited available data regarding HER2 in GEAs and ECAs have considerable variations likely caused by variations in the tumor type selection, testing methods, and scoring criteria. Here, we selected 58 GEA cases to examine the HER2 status using immunohistochemistry and fluorescent in situ hybridization and investigate the prognostic value and their association with other known or potential prognostic factors. When strong complete or lateral/basolateral membranous reactivity in ≥10% tumor cells was used to define HER2 positivity, relatively high prevalence of HER2 overexpression (10/58[17.2%]) and amplification (9/58 [15.5%]), as well as high immunohistochemistry-fluorescent in situ hybridization concordance rate (9/10 [90%]) was found in GEAs. A lateral/basolateral staining pattern ("U-shaped") was observed, at least focally, in most of HER2-positive (3+) and equivocal (2+) tumors. Notably, considerable heterogeneity of HER2 expression was observed in HER2 positive and equivocal cases (80.0% and 83.3%, respectively). HER2 overexpression and amplification were associated with worse progression-free survival (P = .047 and P = .032, respectively). Programmed death-ligand 1 expression was associated with worse progression-free survival (P = .032), whereas mutant-type p53 demonstrated no prognostic significance. Our work laid a solid foundation for the eventual development of a future standard HER2 testing guideline for GEAs.