Nectin-4 and Trop-2 expression in collecting duct carcinoma: new promising therapeutic targets.

BACKGROUND

Collecting duct carcinoma (CDC) is a rare and aggressive renal malignancy with limited therapeutic options and no established biomarker-driven strategies. Given its morphologic and embryologic overlap with urothelial carcinoma, we investigated the expression of Nectin-4 and Trop-2, targets of antibody-drug conjugates (ADCs) with proven activity in urothelial cancer.

PATIENTS AND

METHODS

Tumor samples from 59 patients with CDC who were enrolled in the multicenter CICERONE study (NCT05372302) were centrally reviewed by expert genitourinary pathologists. Immunohistochemical analyses for Nectin-4 and Trop-2 were carried out on formalin-fixed, paraffin-embedded tissue. Tumors were considered positive when >10% of cells showed membranous and/or cytoplasmic staining.

RESULTS

Nectin-4 expression was detected in 41% of cases, with variable staining intensity, while Trop-2 expression was observed in 89% of tumors, frequently showing strong and diffuse staining. No substantial associations were found between marker expression and clinicopathologic features.

CONCLUSIONS

Nectin-4 and Trop-2 are frequently expressed in CDC, supporting a biological overlap with urothelial carcinoma. Although these findings do not imply clinical efficacy, they provide a rationale for prospective evaluation of ADC-based strategies in this rare malignancy, including ongoing clinical trials investigating enfortumab vedotin-based combinations.