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Nuclear E-cadherin Expression is Associated with the Loss of Membranous E-cadherin, Plasmacytoid Differentiation and Reduced Overall Survival in Urothelial Carcinoma of the Bladder

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Loss of E-cadherin represents a hallmark of plasmacytoid differentiation. We analyzed the effect of membranous E-cadherin loss and its nuclear accumulation in patients with locally advanced conventional urothelial carcinoma (UC) who were treated with radical cystectomy and adjuvant chemotherapy.

Methods

A total of 247 formalin-fixed, paraffin-embedded tumor samples were reviewed to detect histological variants of UC. Immunohistochemical staining of E-cadherin was performed and analyzed for membranous and nuclear expression. The correlation between E-cadherin expression and histology was assessed, and overall survival (OS) was analyzed with univariate and multivariate Cox regression and Kaplan–Meier analyses. Correlation of nuclear E-cadherin to tumor stage (pT), lymph node metastasis (pN), histologic subtype, and chemotherapy was performed by Fisher’s exact test.

Results

Membranous and nuclear E-cadherin expression was strongly correlated to plasmacytoid urothelial carcinoma (PUC) (p < 0.001). Complete loss of membranous E-cadherin expression was observed in 76.2 % of PUCs, 11.1 % of conventional UCs, and 0 % of micropapillary urothelial carcinoma (MPCs). Nuclear accumulation was found in 47.6 % of PUCs, 10 % of MPCs, and 1.8 % of UCs. Sixty-two percent of all tumors with negative membranous E-cadherin expression and nuclear accumulation were PUCs (p = 0.035). In a Kaplan–Meier analysis, mean survival with nuclear E-cadherin expression was 31.9 months [95 % confidence interval (CI) 16.1–47.6] of patients without nuclear staining 61 months (95 % CI 53.5–67.7; p = 0.045). A univariate Cox regression analysis showed that nuclear E-cadherin accumulation was associated with a 2-fold increase in risk of death (95 % CI 1.03–4.06; p = 0.04). In multivariate Cox regression analysis adjusted to type of chemotherapy, tumor stage, and tumor grade, the hazard ratio for patients with nuclear E-cadherin was 2.03 (95 % CI 1.00–4.121; p = 0.050).

Conclusions

Nuclear E-cadherin is associated with PUCs and is suggested to be an independent prognostic factor in advanced UC.

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Authors and Affiliations

  1. Department of Urology, University Hospital Erlangen, Erlangen, Germany

    Bastian Keck MD, Sven Wach PhD, Frank Kunath MD, Helge Taubert PhD & Bernd Wullich MD

  2. Department of Pathology, University Erlangen, Erlangen, Germany

    Simone Bertz MD & Arndt Hartmann MD

  3. Urology Practice, Prüner Gang, Kiel, Germany

    Jan Lehmann MD

  4. Department of Urology, Saarland University, Homburg, Germany

    Michael Stöckle MD

Authors
  1. Bastian Keck MD
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  2. Sven Wach PhD
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  3. Frank Kunath MD
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  4. Simone Bertz MD
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  5. Helge Taubert PhD
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  6. Jan Lehmann MD
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  7. Michael Stöckle MD
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  8. Bernd Wullich MD
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  9. Arndt Hartmann MD
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Correspondence to Bastian Keck MD.

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Keck, B., Wach, S., Kunath, F. et al. Nuclear E-cadherin Expression is Associated with the Loss of Membranous E-cadherin, Plasmacytoid Differentiation and Reduced Overall Survival in Urothelial Carcinoma of the Bladder. Ann Surg Oncol 20, 2440–2445 (2013). https://doi.org/10.1245/s10434-012-2709-4

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  • DOI: https://doi.org/10.1245/s10434-012-2709-4

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