HER2-low and HER2-ultra-low salivary gland carcinomas: an exploratory study

The promising efficacy of novel anti-HER2 antibody-drug conjugates in breast cancer has led to the recognition of HER2-low and HER2-ultra-low in advanced solid tumors, including salivary gland carcinomas. In this study, we explore the frequency of HER2-low and HER2-ultra-low immunoexpression in a retrospective cohort of 81 salivary gland carcinomas, including 35 salivary duct carcinomas (SDC) and 46 non-SDCs. HER2 immunohistochemistry was interpreted according to ASCO/CAP guidelines. Among SDCs, the frequency of HER2-positive (3 +), HER2-low (1 + and 2 +), and HER2-ultra-low (0 +) was 34%, 63%, and 0%, respectively. None of the non-SDCs was HER2-positive (3 +). The rate of HER2 2 + , 1 + , and 0 + was 4%, 32%, and 24%, respectively, in non-SDCs. HER2-low (1 + or 2 +) was seen in 62% of myoepithelial carcinomas, 0% of adenoid cystic carcinomas, 56% of acinic cell carcinomas, and 33% of carcinomas not otherwise specified. HER2-ultra-low (0 +) was observed in 23% of myoepithelial carcinomas, 33% of adenoid cystic carcinomas, 22% of acinic cell carcinomas, and 11% of carcinomas not otherwise specified. Although HER2-positive (3 +) was seen only in SDC, HER2-low and HER2-ultra-low expressions were not uncommon across salivary gland carcinomas, including SDCs and various non-SDC types. These findings suggest the potential applicability of HER2-targeted therapy in salivary gland carcinomas.