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Open AccessArticle

Expression of Nectin-4 and PD-L1 in Upper Tract Urothelial Carcinoma

1
Department of Urology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
2
Department of Urology, Kindai University Faculty of Medicine, 377-2, Ohno-Higashi, Sayama, Osaka 589-8511, Japan
3
Department of Pathology, Johns Hopkins University, Baltimore, MD 21287, USA
4
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35233-7331, USA
5
Department of Pathology, Kidney Diseases Research Center, Isfahan University of Medical Sciences, Isfahan 8174673461, Iran
6
Department of Urological Immuno-Oncology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
7
Department of Urology, Osaka General Medical Center, Osaka 558 8558, Japan
8
Department of Pathology, Osaka General Medical Center, Osaka 558 8558, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(15), 5390; https://doi.org/10.3390/ijms21155390
Received: 3 July 2020 / Revised: 20 July 2020 / Accepted: 27 July 2020 / Published: 29 July 2020
(This article belongs to the Special Issue Biomarker-Oriented Treatment of Urogenital Cancers)
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. View Full-Text
Keywords: Nectin-4; Programmed Death Ligand 1; upper tract urothelial carcinoma; enfortumab vedotin Nectin-4; Programmed Death Ligand 1; upper tract urothelial carcinoma; enfortumab vedotin
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MDPI and ACS Style

Tomiyama, E.; Fujita, K.; Rodriguez Pena, M.D.C.; Taheri, D.; Banno, E.; Kato, T.; Hatano, K.; Kawashima, A.; Ujike, T.; Uemura, M.; Takao, T.; Yamaguchi, S.; Fushimi, H.; Yoshimura, K.; Uemura, H.; Netto, G.J.; Nonomura, N. Expression of Nectin-4 and PD-L1 in Upper Tract Urothelial Carcinoma. Int. J. Mol. Sci. 2020, 21, 5390. https://doi.org/10.3390/ijms21155390

AMA Style

Tomiyama E, Fujita K, Rodriguez Pena MDC, Taheri D, Banno E, Kato T, Hatano K, Kawashima A, Ujike T, Uemura M, Takao T, Yamaguchi S, Fushimi H, Yoshimura K, Uemura H, Netto GJ, Nonomura N. Expression of Nectin-4 and PD-L1 in Upper Tract Urothelial Carcinoma. International Journal of Molecular Sciences. 2020; 21(15):5390. https://doi.org/10.3390/ijms21155390

Chicago/Turabian Style

Tomiyama, Eisuke; Fujita, Kazutoshi; Rodriguez Pena, Maria D.C.; Taheri, Diana; Banno, Eri; Kato, Taigo; Hatano, Koji; Kawashima, Atsunari; Ujike, Takeshi; Uemura, Motohide; Takao, Tetsuya; Yamaguchi, Seiji; Fushimi, Hiroaki; Yoshimura, Kazuhiro; Uemura, Hirotsugu; Netto, George J.; Nonomura, Norio. 2020. "Expression of Nectin-4 and PD-L1 in Upper Tract Urothelial Carcinoma" Int. J. Mol. Sci. 21, no. 15: 5390. https://doi.org/10.3390/ijms21155390

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