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

Ricardo L. Favaretto, Atessa Bahadori, Romain Mathieu, Andrea Haitel, Bernhard Grubmüller, Vitaly Margulis, Jose A. Karam, Morgan Rouprêt, Christian Seitz, Pierre I. Karakiewicz, Isabela W. Cunha, Stenio C. Zequi, Christopher G. Wood, Alon Z. Weizer, Jay D. Raman, Mesut Remzi, Nathalie Rioux-Leclercq, Solene Jacquet-Kammerer, Karim Bensalah, Yair LotanAlexander Bachmann, Michael Rink, Alberto Briganti, Shahrokh F. Shariat

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Abstract

Purpose: To assess the role of E-cadherin as prognostic biomarker in upper tract urothelial carcinoma (UTUC) in a large multi-institutional cohort of patients. Methods: Immunohistochemistry technique was used to evaluate E-cadherin expression in 678 patients with unilateral, sporadic UTUC treated with RNU. E-cadherin expression was considered decreased if 10 % or more cells had decreased expression (<90 %). Results: Decreased E-cadherin expression was observed in 353 patients (52.1 %) and was associated with advanced pathological stage (P < 0.001), higher grade (P < 0.001), lymph node metastasis (P = 0.006), lymphovascular invasion (P < 0.001), concomitant carcinoma in situ (P < 0.001), multifocality (P = 0.004), tumor necrosis (P = 0.020) and sessile architecture (P < 0.001). Within a median follow-up of 30 months (interquartile range 15–57), 171 patients (25.4 %) experienced disease recurrence and 150 (21.9 %) died from UTUC. In univariable analyses, decreased E-cadherin expression was significantly associated with worse recurrence-free survival (P < 0.001) and cancer-specific survival CSS (P = 0.006); however, in multivariable analyses, it was not (P = 0.74 and 0.84, respectively). The lack of independent prognostic value of E-cadherin remained true in all subgroup analyses. Conclusion: In UTUC patients treated with RNU, decreased E-cadherin expression is associated with features of biologically and clinically aggressive disease and worse outcome in univariable, but not multivariable, analyses. If E-cadherin’s association with factors of advanced disease is confirmed on UTUC biopsy specimens, it could be used to help in the clinical decision-making regarding kidney-sparing approaches and/or neo-adjuvant chemotherapy.

Original languageEnglish (US)
Pages (from-to)113-120
Number of pages8
JournalWorld Journal of Urology
Volume35
Issue number1
DOIs
StatePublished - Jan 1 2017

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All Science Journal Classification (ASJC) codes

  • Urology

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Favaretto, R. L., Bahadori, A., Mathieu, R., Haitel, A., Grubmüller, B., Margulis, V., Karam, J. A., Rouprêt, M., Seitz, C., Karakiewicz, P. I., Cunha, I. W., Zequi, S. C., Wood, C. G., Weizer, A. Z., Raman, J. D., Remzi, M., Rioux-Leclercq, N., Jacquet-Kammerer, S., Bensalah, K., ... Shariat, S. F. (2017). Prognostic role of decreased E-cadherin expression in patients with upper tract urothelial carcinoma: a multi-institutional study. World Journal of Urology, 35(1), 113-120. https://doi.org/10.1007/s00345-016-1835-1