Faculty, Staff and Student Publications

Language

English

Publication Date

9-1-2025

Journal

Journal of Oral Pathology & Medicine

DOI

10.1111/jop.70008

PMID

40624990

PMCID

PMC12419983

PubMedCentral® Posted Date

7-8-2025

PubMedCentral® Full Text Version

Post-print

Abstract

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.

Keywords

Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Antigens, Neoplasm, Biomarkers, Tumor, Carcinoma, Adenoid Cystic, Cell Adhesion Molecules, Cell Line, Tumor, Immunoconjugates, Immunohistochemistry, Salivary Gland Neoplasms, Tissue Array Analysis, ADC, adenoid cystic carcinoma, antibody–drug conjugate, immunohistochemistry, sacituzumab govitecan, SN‐38, TROP2

Comments

Trial registration: clinicaltrials.gov: NCT05884320; NCI-2023-04260.

Published Open-Access

yes

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