Expression and Prognostic Significance of Different Antibody-Drug Conjugate Target Proteins in Urachal Carcinoma

Urachal carcinoma (UrC), a rare malignancy originating from urachal remnants, currently lacks standardized therapeutic options for advanced stages. While antibody-drug conjugate (ADC) therapy has emerged as a transformative approach in oncology, its clinical application in UrC remains investigational due to the paucity of data regarding target antigen expression profiles. This study systematically characterized the immunohistochemical landscape of UrC through the lens of established ADC targets and evaluated their prognostic implications, thereby informing future therapeutic development.

We retrospectively analyzed 41 histologically confirmed UrC specimens with complete clinical information. Immunohistochemical evaluation was performed for 6 therapeutic targets: HER2, Nectin-4, Claudin18.2, Trop2, Mesothelin, and PD-L1. Standardized scoring system was used to quantify the level of target expression and to determine the rate of high expression for each target. Survival outcomes were assessed through Kaplan-Meier method and Cox proportional hazards modeling.

With a median follow-up of 99 months, the cohort exhibited a 5-year overall survival (OS) rate of 62.4% (95% CI, 48.5%-80.3%). Analysis of ADC target protein expression showed that Trop2 had the highest rate of high expression (58.5%), followed by Mesothelin (43.9%), Claudin18.2 (34.1%), Nectin-4 (24.4%), HER2 (9.8%), and PD-L1 (4.9%). Survival analysis demonstrated significantly reduced 5-year overall survival (OS) in the Trop2-high group (47.1% vs. 87.5%, P = 0.01). Multivariate Cox regression analysis identified both Trop2 and Sheldon stage as independent prognostic determinants.

Our findings confirm that UrC has the potential to be treated by ADC. Trop2 has the highest high expression rate in UrC and is associated with a worse prognosis, which may be a potential target for ADC therapy for UrC.