ERBB2 amplification and HER2 expression in salivary duct carcinoma: Evaluation of scoring guidelines and potential for expanded anti-HER2 therapy

Salivary duct carcinoma (SDC) is aggressive with limited therapeutic options. A subset of SDC display human epidermal growth factor receptor 2 (HER2) protein overexpression by immunohistochemistry, and some show ERBB2gene amplification. Guidelines for HER2 scoring are not firmly established. Recent advances in breast carcinoma have established a role for anti-HER2 therapies in lesions with low HER2 expression lacking ERBB2amplification. Delineating HER2 staining patterns in SDC is critical for evaluating anti-HER2 treatments. 53 cases of SDC resected at our institution between 2004 and 2020 were identified. Androgen receptor (AR) and HER2 immunohistochemistry and ERBB2FISH were performed in all cases. AR expression was scored for percent positive cells and categorized as positive (>10% of cells), low positive (1-10%), or negative (<1%). HER2 staining levels and patterns were recorded, scored using 2018 ASCO/CAP guidelines, and categorized into HER2-positive (3+ or 2+ with ERBB2amplification), HER2-low (1+ or 2+ without ERBB2amplification), HER2-very low (faint staining in <10% of cells), or HER2-absent. Clinical parameters and vital status were recorded. Median age was 70 years with a male predominance. ERBB2-amplified tumors (11/53; 20.8%) presented at lower pT stages (pTis/pT1/pT2, p= 0.005, Fisher exact test) and more frequently had perineural invasion (p= 0.007, Fisher exact test) compared with ERBB2non-amplified tumors; no other pathologic features differed significantly by gene amplification status. 2+ HER2 staining by 2018 ASCO/CAP criteria was most common (26/53; 49%); only 4 cases (8%) were HER2-absent. 3+ HER2 staining was found in 9 tumors and all were ERBB2-amplified. 6 patients with HER2-expressing tumors received trastuzumab therapy, including 2 with ERBB2-amplified tumors. Overall survival and recurrence-free survival did not differ significantly based on ERBB2status. This work suggests that 2018 ASCO/CAP guidelines for HER2 evaluation in breast carcinoma could be applied to SDC. Our findings also show broad overexpression of HER2 in SDC raising the possibility that more patients may benefit from anti-HER2 directed therapies.