Expression characteristics of clinically relevant antibody-drug conjugate targets in gestational trophoblastic...

Antibody-drug conjugates (ADCs) have demonstrated clinical benefit in a variety of malignancies. However, information regarding ADC target expression in gestational trophoblastic neoplasia (GTN) remains scarce. This study aimed to characterize the immunohistochemical expression patterns of clinically relevant ADC targets in GTN and to assess their potential translational relevance.

Immunohistochemistry was performed on tumor tissues from 33 patients with GTN, including 16 choriocarcinomas, 6 placental site trophoblastic tumors, and 11 epithelioid trophoblastic tumors. Additionally, 10 normal placental tissues and 5 complete hydatidiform mole specimens were included. Expression of the following ADC targets was evaluated: FOLR1, Nectin4, TROP2, CEACAM5, HER3, CLDN6, CLDN18.2, and tissue factor. Target expression was assessed based on membranous staining using H-score methodology, and FOLR1 expression was additionally evaluated using PS2+ criteria. Associations with clinicopathologic parameters were examined.

Nectin4 was detected in all GTN cases, with medium-to-high expression observed in 81.8% of tumors. FOLR1 was positive in 90.9% of cases, with high expression identified in 36.4% using PS2+ criteria. TROP2, CEACAM5, HER3, CLDN6, and tissue factor showed variable and generally low-to-moderate expression, whereas CLDN18.2 was consistently absent. TROP2 expression differed significantly among GTN subtypes and was highest in epithelioid trophoblastic tumor. No significant associations were observed between ADC target expression and FIGO stage, prognostic score, prior therapy, recurrence, or disease-specific mortality.

GTN exhibits frequent expression of several established ADC targets, particularly Nectin4 and FOLR1. These findings provide a molecular rationale for biomarker-driven investigation of ADC-based therapeutic strategies in refractory or recurrent GTN.