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Nectin-4 Expression and Prognosis in Upper Tract Urothelial Cancer

By: Lauren Harrison, MS
Posted: Wednesday, October 13, 2021

Nectin-4 is a cell-adhesion molecule expressed in various cancers, including breast, lung, pancreatic, and bladder. Strong expression of Nectin-4 appears to be associated with a poorer prognosis in patients with upper tract urothelial carcinomas, according to an abstract presented during the 2021 American Urological Association (AUA) Annual Meeting (Abstract PD42-07) and published in The Journal of Urology.

“Enfortumab vedotin [which targets Nectin-4] may be effective in a broad range of patients with upper tract urothelial carcinoma regardless of PD-L1 expression level,” concluded Kazutoshi Fujita, MD, PhD, of Osaka University, Japan, and colleagues.

Researchers created upper tract urothelial tumor microarrays, pairing 99 normal-appearing urothelial tissues from patients with nonmetastatic upper tract urothelial carcinoma with invasive components of urothelial tumors. Immunohistochemical analysis was then performed on these samples to assess the expression of both PD-L1 and Nectin-4.

A majority (65.7%) of the tumor samples showed expression of Nectin-4, which was significantly different from the normal tissue (P <.001). PD-L1 expression was detected in 24.2% of samples; however, there did not appear to be any correlation between Nectin-4 and PD-L1 expression. Patients whose tumor samples had strong expression of Nectin-4 had a significantly higher risk of tumor progression (P = .031) and cancer-specific mortality (P = .036).

A subgroup of samples was taken from patients deemed to be at high risk. These patients had lymphovascular invasion, lymph node metastases, or pathologic stage T3 cancer or higher. Strong Nectin-4 expression was an independent predictor of tumor progression (hazard ratio = 3.32, P =.027).

Disclosure: The study authors reported no conflicts of interest.



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