Prognostic role of expression of N-cadherin in patients with upper tract urothelial carcinoma: a multi-institutional study

Mohammad Abufaraj,Mehmet Özsoy,Kilian Gust,Morgan Rouprêt,Marco Moschini,Jose A Karam,Shahrokh F Shariat,Karim Bensalah,Christopher G Wood,Romain Mathieu,Vitaly Margulis,Alberto Briganti,Francesco Soria,Andrea Haitel

doi:10.1007/s00345-016-1968-2

Abstract

PurposeTo assess the role of N-cadherin as prognostic biomarker in patients with upper tract urothelial carcinoma (UTUC) in a large multi-institutional cohort of patients.Patients and methodsImmunohistochemistry was used to evaluate the status of N-cadherin expression in 678 patients with unilateral sporadic UTUC treated with radical nephroureterectomy. N-cadherin was considered positive if any immunoreactivity with membranous staining was detected. The Kaplan–Meier method was used to estimate recurrence-free survival, overall survival and cancer-specific survival. Disease recurrence, overall mortality and cancer-specific mortality probabilities were tested in Cox regression models.ResultsExpression of N-cadherin was observed in 292 (43.1%) of patients, and it was associated with advanced tumour stage (p < 0.04), lymph node metastases (p = 0.04) and sessile architecture (p < 0.02). Within a median follow-up of 37.5 months (IQR 20–66), 171 patients (25.2%) experienced disease recurrence and 150 (22.1%) died from UTUC. In univariable analyses, N-cadherin expression was significantly associated with higher probability of recurrence (p = 0.01), but not overall (p = 0.9) or cancer-specific mortality (p = 0.06). When adjusted for the effects of all available confounders, N-cadherin was not associated with any of the survival outcomes.ConclusionN-cadherin is expressed in approximately 2/5 of UTUs. It is associated with adverse pathologic factors but not with survival outcomes. Its clinical value remains limited.

Highlights

Upper tract urothelial carcinoma (UTUC) is a relatively rare entity that represents 5–10% of Urothelial carcinoma (UC) with an estimated incidence of 1–2 cases per 100,000 inhabitants in western countries [1, 2]
Most patients underwent open Radical nephroureterectomy (RNU) (78.5%), lymphadenectomy was performed in 22.9% of patients, and adjuvant chemotherapy was given in 10% of patients
To test the value of one biomarker for this purpose, we performed a retrospective multicenter study in which we evaluated the association of N-cadherin expression status with clinicopathologic features and prognostic outcomes in 678 patients treated with RNU for UTUC

Summary

Introduction

Upper tract urothelial carcinoma (UTUC) is a relatively rare entity that represents 5–10% of Urothelial carcinoma (UC) with an estimated incidence of 1–2 cases per 100,000 inhabitants in western countries [1, 2]. It is still considered an aggressive disease with a high incidence of disease progression and mortality [3, 4]. Current prognostic and predictive tools based on standard clinicopathological factors remain insufficient to yield enough accuracy for clinical decision-making [4, 7]. Molecular markers associated with clinically significant outcome may help improve our current prognostication

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