909P TROP2 expression in salivary gland adenoid cystic carcinoma (ACC): A new potential therapeutic target for the non-solid subtype

ACC is a neoplasm of salivary gland (SsG) characterized by biphasic ductal and myoepithelial components and solid, cribriform, and/or tubular architectural patterns (AP). Based on clinical and transcriptional features, two distinct subtypes are described: ACC-I (aggressive and mostly comprised of solid AP) and ACC-II (indolent and mainly represented by tubular and cribriform AP). Our ACC transcriptomic analysis revealed that TROP2 is upregulated, especially in the ACC-II subtype. TROP2 is a transmembrane glycoprotein involved in oncogenic pathways. Sacituzumab govitecan (SG) is an antibody-drug conjugate (ADC) targeting TROP2 that showed promising results in metastatic breast cancer. Despite the clinical and biological heterogeneity of ACC, there is no difference in therapeutic strategies and no standard treatment for recurrent/metastatic (R/M) disease. Hence, we aimed to investigate TROP2 as a potential target for ACC. Immunohistochemistry for TROP2 (EPR20043, 1:4000) was performed in a tissue microarray and manually scored as negative (< 1% of any intensity), weak (≤ 70% of weak or ≤ 30% of moderate expression), moderate (> 70% of weak or >30% of moderate or ≤ 30% of strong expression), and high (>70% of moderate or >30% of strong expression). The AP was grouped as non-solid (NS, tubular and/or cribriform), predominant solid (S), or S+NS subtypes. A TROP2 expressing ACC cell line from a PDX organoid was treated with SG for 72hrs, and viability was assessed through luminescent cell viability assay. Out of 165 ACCs, 64% were from minor and 24% from major SsG and 13% from other secretory glands. TROP2 expression was high in 59%, moderate in 30%, weak in 8%, and negative in 3%. NS ACC AP was significantly correlated (p<0.001) with high (73%) expression of TROP2 compared to S+NS (12% high) and S (17% high). SG impaired the viability of the ACC TROP2-positive cell line. TROP2 is widely expressed in ACC, mainly in non-solid AP, and an anti-proliferative effect was observed in an ACC cell line treated with TROP2-ADC SG. Therefore, we provide a biological rationale for using TROP2 as a potential target for R/M ACC.