Clinical implication of the mammalian target of rapamycin pathway in upper tract urothelial carcinoma with negative GATA binding protein 3 expression

Yamamoto, Yorimasa; Fujita, Kazutoshi; Munari, Enrico; Uemura, Mamoru; Miyamoto, Hiroshi; Netto, George J.

doi:10.1111/iju.13940

Cited by 2 publications

(1 citation statement)

References 7 publications

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“…The UTUC TMA was constructed with spotted triplicate urothelial tumor samples (from dominant tumors/invasive components if present) and paired normal-appearing urothelial tissues (from the renal pelvis and ureter) obtained from 99 patients with non-metastatic UTUC, who underwent radical nephroureterectomy performed at Osaka General Medical Center, Osaka between 1997 and 2011, as described previously [ 18 , 19 , 20 , 21 , 22 ]. Appropriate approval was obtained from the local institutional review board (Osaka General Medical Center Institutional Review Board, Protocol Number: 25-2014, 19 June 2013) before construction and use of the TMA, and written informed consent was obtained from all patients.…”

Section: Methodsmentioning

confidence: 99%

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

Tomiyama

Fujita

Peña

et al. 2020

IJMS

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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.

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