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


METHODS
Immunohistochemistry 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.


RESULTS
Expression 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.


CONCLUSIONS
N-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.
Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
Mohammad
M
Abufaraj
Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.|Department of Urology, Urological Research Institute, San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy.
Marco
M
Moschini
Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.|Division of Urology, Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of Torino, Turin, Italy.
Francesco
F
Soria
Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
Kilian
K
Gust
Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.|Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria.
Mehmet
M
Özsoy
Department of Urology, University of Rennes, Rennes, France.
Romain
R
Mathieu
Department of Urology, Pitié-Salpétrière, Assistance-Publique Hôpitaux de Paris, Faculté de Médecine Pierre et Marie Curie, University Paris VI, Paris, France.
Morgan
M
Rouprêt
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Vitaly
V
Margulis
Department of Urology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Jose A
JA
Karam
Department of Urology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Christopher G
CG
Wood
Department of Urology, Urological Research Institute, San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy.
Alberto
A
Briganti
Department of Urology, University of Rennes, Rennes, France.
Karim
K
Bensalah
Department of Pathology, Medical University of Vienna, Vienna, Austria.
Andrea
A
Haitel
Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria. sfshariat@gmail.com.|Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA. sfshariat@gmail.com.|Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria. sfshariat@gmail.com.|Department of Urology, Weill Cornell Medical College, New York, NY, USA. sfshariat@gmail.com.
Shahrokh F
SF
Shariat
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D002277:Carcinoma / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000473:pathology; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D000074682:Nephroureterectomy / Q000379:methods / Q000706:statistics & numerical data; D011237:Predictive Value of Tests; D011379:Prognosis; D014513:Ureter / Q000473:pathology; D014516:Ureteral Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D019459:Urothelium / Q000473:pathology*
D014408:Biomarkers, Tumor; D015820:Cadherins
N-Cadherin; Prediction; Survival; UTUC prognosis; Upper tract urothelial carcinoma; Urothelial carcinoma