Enfortumab vedotin is a novel antibody-drug conjugate targeting Nectin-4, which is highly expressed in urothelial carcinoma. However, the expression status of Nectin-4 in upper tract urothelial carcinoma (UTUC) remains unclear. The relationship between Nectin-4 and Programmed Death Ligand 1 (PD-L1) in UTUC is also ambiguous. We performed immunohistochemical analysis of 99 UTUC tissue microarray to assess the expression of Nectin-4 and PD-L1 in UTUC. Nectin-4-positivity was detected in 65 (65.7%) samples, and PD-L1 was detected in 24 (24.2%) samples. There was no correlation between the expression of Nectin-4 and PD-L1. Patients with strong Nectin-4-expressing tumors had a significantly higher risk of progression (p = 0.031) and cancer-specific mortality (p = 0.036). Strong Nectin-4 expression was also an independent predictor of disease progression in the high-risk group (pT3 ≤ or presence of lymphovascular invasion or lymph node metastasis) (Hazard ratio, 3.32 [95% confidence interval, 1.20-7.98; p = 0.027]). In conclusion, we demonstrated that Nectin-4 expression rate in UTUC was 65.7% and independent of PD-L1 expression. Strong Nectin-4 expression was associated with worse progression-free survival in high-risk UTUC. These findings suggested that enfortumab vedotin may be effective in a broad range of patients with UTUC, regardless of PD-L1 expression.
International journal of molecular sciences. 2020 Jul 29*** epublish ***
Eisuke Tomiyama, Kazutoshi Fujita, Maria Del Carmen Rodriguez Pena, Diana Taheri, Eri Banno, Taigo Kato, Koji Hatano, Atsunari Kawashima, Takeshi Ujike, Motohide Uemura, Tetsuya Takao, Seiji Yamaguchi, Hiroaki Fushimi, Kazuhiro Yoshimura, Hirotsugu Uemura, George J Netto, Norio Nonomura
Department of Urology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan., Department of Pathology, Johns Hopkins University, Baltimore, MD 21287, USA., Department of Urology, Kindai University Faculty of Medicine, 377-2, Ohno-Higashi, Sayama, Osaka 589-8511, Japan., Department of Urology, Osaka General Medical Center, Osaka 558 8558, Japan., Department of Pathology, Osaka General Medical Center, Osaka 558 8558, Japan.