Dysregulation of β-catenin is an independent predictor of oncologic outcomes in patients with clear cell renal cell carcinoma

Laura Maria Krabbe, Mary E. Westerman, Aditya Bagrodia, Bishoy A. Gayed, Oussama M. Darwish, Ahmed Q. Haddad, Dina Khalil, Payal Kapur, Arthur I Sagalowsky, Yair Lotan, Vitaly Margulis

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Purpose Epithelial-to-mesenchymal transition is thought to have a crucial role in cancer progression and metastatic egress. We evaluated the association of β-catenin, an important mediator of epithelial-to-mesenchymal transition, with pathological parameters and oncologic outcomes in patients with clear cell renal cell carcinoma. Materials and Methods Immunohistochemical staining was performed for β-catenin on tissue microarrays of patients with nonmetastatic clear cell renal cell carcinoma. Membranous and cytoplasmic expression patterns were assessed separately. β-Catenin was considered dysregulated if membranous as well as cytoplasmic expression was abnormal. Groups were compared based on normal vs dysregulated β-catenin. Survival probabilities were assessed by the Kaplan-Meier method. Cox proportional hazard models were used to identify predictors of oncologic outcomes. Results Included in the study were 406 patients with a median followup of 58 months. Of the patients 52 (12.8%) and 25 (6.2%) experienced recurrence and died of clear cell renal cell carcinoma, respectively. β-Catenin was dysregulated in 70 patients (17.2%). Dysregulation was uniformly associated with adverse pathological features, including advanced T stage, larger tumor diameter, nodal positivity, higher Fuhrman grade, tumor thrombus, sarcomatoid features, necrosis and lymphovascular invasion (each p <0.001). Patients with dysregulated β-catenin had inferior recurrence-free and cancer specific survival (each p <0.001). On multivariate analysis adjusting for tumor stage, nodal status and grade dysregulation was an independent predictor of recurrence-free and cancer specific survival (HR 2.2, 95% CI 1.2-3.9, p = 0.008 and HR 2.4, 95% CI 1.1-5.6, p = 0.044, respectively). Conclusions Dysregulation of β-catenin may be an important phenomenon in clear cell renal cell carcinoma carcinogenesis. These findings support further study of β-catenin, and systematic assessment of β-catenin and epithelial-to-mesenchymal transition in clear cell renal cell carcinoma.

Original languageEnglish (US)
Pages (from-to)1671-1677
Number of pages7
JournalJournal of Urology
Volume191
Issue number6
DOIs
StatePublished - Jun 2014

Keywords

  • beta catenin
  • carcinogenesis
  • carcinoma
  • epithelial-mesenchymal transition
  • kidney
  • renal cell

ASJC Scopus subject areas

  • Urology

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