Dysregulation of β-Catenin is an Independent Predictor of Oncologic Outcomes in Patients with Clear Cell Renal Cell Carcinoma

• Published in: The Journal of urology Vol. 191; no. 6; pp. 1671 - 1677
• Main Authors: Krabbe, Laura-Maria, Westerman, Mary E, Bagrodia, Aditya, Gayed, Bishoy A, Darwish, Oussama M, Haddad, Ahmed Q, Khalil, Dina, Kapur, Payal, Sagalowsky, Arthur I, Lotan, Yair, Margulis, Vitaly
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2014; Elsevier
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; beta catenin; beta Catenin - biosynthesis; Biological and medical sciences; Biomarkers, Tumor - metabolism; carcinogenesis; carcinoma; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - mortality; Carcinoma, Renal Cell - pathology; Epithelial-Mesenchymal Transition; Female; Follow-Up Studies; Humans; Immunohistochemistry; kidney; Kidney Neoplasms - metabolism; Kidney Neoplasms - mortality; Kidney Neoplasms - pathology; Kidneys; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Recurrence, Local - metabolism; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - pathology; Nephrology. Urinary tract diseases; Prognosis; renal cell; Retrospective Studies; Survival Rate; Time Factors; Tumors; Tumors of the urinary system; United States - epidemiology; Urology; Young Adult; United States; CSS; cancer specific survival; beta catenin; clear cell RCC; EMT; epithelial-to-mesenchymal transition; kidney; renal cell; renal cell carcinoma; ccRCC; RCC; carcinogenesis; lymphovascular invasion; carcinoma; recurrence-free survival; epithelial-mesenchymal transition; LVI; RFS; Nephrology; Prognosis; Cell transformation; Carcinogenesis; Kidney; Urology; Beta; Dicotyledones; Angiospermae; Grawitz tumor; Kidney disease; Human; Urinary system disease; Mesonephroma; Malignant tumor; Chenopodiaceae; Clear cell carcinoma; Urinary system; Kidney cancer; β Catenin; Spermatophyta; Epithelial mesenchymal transition; Predictive factor; Cancer
• ISSN: 0022-5347; 1527-3792
• DOI: 10.1016/j.juro.2013.11.052

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.