Prognostic Role of Decreased E-cadherin Expression in Patients With Upper Tract Urothelial Carcinoma: A Multi-Institutional Study

World J Urol. 2017 Jan;35(1):113-120. doi: 10.1007/s00345-016-1835-1. Epub 2016 Apr 29.

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.

Keywords: Carcinoma; E-cadherin; Prediction; Prognosis; Recurrence; Survival; Urothelium.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Antigens, CD
  • Cadherins / metabolism*
  • Carcinoma in Situ / complications
  • Carcinoma in Situ / metabolism*
  • Carcinoma in Situ / pathology
  • Carcinoma, Transitional Cell / metabolism*
  • Carcinoma, Transitional Cell / mortality
  • Carcinoma, Transitional Cell / pathology
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Lymph Nodes / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Grading
  • Neoplasm Staging
  • Neoplasms, Multiple Primary / metabolism*
  • Neoplasms, Multiple Primary / mortality
  • Neoplasms, Multiple Primary / pathology
  • Prognosis
  • Retrospective Studies
  • Ureteral Neoplasms / metabolism*
  • Ureteral Neoplasms / mortality
  • Ureteral Neoplasms / pathology

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins