TROP2 Expression in Salivary Gland Adenoid Cystic Carcinoma (ACC) According to Histologic Subtype: Therapeutic Implications.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a common salivary gland carcinoma with high recurrence and distant metastasis rates. Currently, there is no standard systemic treatment available. TROP2 is a transmembrane glycoprotein involved in the oncogenesis of several tumors that can be therapeutically targeted by a TROP2-antibody-drug conjugate (ADC). We aimed to characterize TROP2 expression in ACC and assess TROP2 as a potential therapeutic target. METHODS: TROP2 immunohistochemistry was performed in a tissue microarray including 165 ACC of salivary gland. The tumors were grouped according to the histological pattern as non-solid, solid + non-solid, or solid. TROP2 protein expression in ACC cell lines was assessed and subjected to drug screening with TROP2-ADC. RESULTS: TROP2 expression was high in 59%, moderate in 30%, weak in 8%, and negative in 3% of cases. TROP2 expression was significantly higher in non-solid compared with solid or solid + non-solid (p < 0.001). Notably, TROP2 expression was heterogenous among the dual cellular component, with TROP2 expression identified predominantly in the ductal and not in the myoepithelial cells. In vitro drug screening demonstrated that TROP2-ADC had selective anti-tumor effect in TROP2 expressing ACC cells. CONCLUSIONS: TROP2 expression is prevalent in ACC, particularly in the ductal cell component of the non-solid tumors. The pre-clinical drug screening findings provide a biological rationale for exploring TROP2 as a therapeutic target in TROP2-expressing ACC. TRIAL REGISTRATION: clinicaltrials.gov: NCT05884320; NCI-2023-04260.