Dr. Ghali on Nectin-4 and TROP-2 Expression in Urothelial, Variant Histology Bladder Cancer

Fady Ghali, MD, acting instructor, Urologic Oncology, Department of Urology, University of Washington, discusses the expression of Nectin-4 and TROP-2 in variant histology bladder cancer and urothelial cancer.

Nectin-4 and TROP-2 are cell surface targets for the antibody-drug conjugates enfortumab vedotin (Padcev) and sacituzumab govitecan-hziy (Trodelvy), respectively, which are both FDA approved for the treatment of patients with locally advanced/metastatic urothelial cancer. During the 2022 American Urological Association Annual Meeting, Ghali shared findings from an analysis that evaluated the expression levels of Nectin-4 and TROP-2 in histologic variants of bladder cancer within primary and matched metastatic samples.

Data showed that in plasmacytoid urothelial cancer and squamous cell carcinoma, moderate to high levels of Nectin-4 and TROP-2 were expressed, Ghali says; however, neuroendocrine tumors were not found to express these markers. Additionally, plasmacytoid urothelial cancer and urothelial cancer with squamous differentiation expressed Nectin-4 and TROP-2 at both the primary and metastatic sites, Ghali adds.

Notably, the distribution of Nectin-4 was relatively even between the membrane and the cytoplasm, Ghali adds. In plasmacytoid urothelial cancer and urothelial cancer with squamous differentiation, primary tumors had higher levels of Nectin-4 expressed on the membrane; however, in the matched metastatic tumors, Nectin-4 was found to be concentrated in the cytoplasm, Ghali says. TROP-2 did not follow the same pattern; high levels of this marker were found in the membrane and cytoplasm for both primary and metastatic sites, Ghali concludes.