Aberrant Β-Catenin Expression is Related to Invasive Tumor Growth in Urothelial Carcinoma of the Urinary Bladder

β-Catenin is a dual function protein with roles in cell cohesion and as a critical intracellular signal transducer in the Wnt signaling pathway. Cytoplasmic and nuclear translocation of the β-Catenin protein results in an increased transcription of cancer promoting genes. To study the prevalence and the potential role of aberrant β-Catenin staining patterns, more than 2,700 bladder tumors were analyzed by immunohistochemistry (IHC) in a tissue microarray format. The cohort included 636 patients with radical cystectomy for muscle-invasive disease (pT2-4) for which follow-up data were available. In normal urothelium, β-Catenin staining was always strong and largely limited to the cell membranes. A comparable staining pattern was also seen in the overwhelming majority of non-invasive pTa tumors, especially in case of low-grade neoplasms. Aberrant β-Catenin staining patterns were observed in 20.3% of tumors and included unequivocal (2.8%) and equivocal nuclear/cytoplasmic staining (10.6%), complete loss of β-Catenin staining (1.5%), and reduced β-Catenin staining (1+, 5.4%). β-Catenin staining was heterogeneous in 20.8%. All aberrant β-Catenin staining patterns were associated with invasive tumor growth (p = < 0.0001–0.0006), but unrelated to survival of patients with pT2-4 cancers. A complete loss of membranous β-Catenin staining was linked to UICC stage (p = 0.0106) and within pT2-4 tumors, to high pN (p = 0.0014) and pT p = 0.0100). Associations also occurred between heterogeneity and nodal metastasis (p = 0.0207), equivocal nuclear/cytoplasmic staining and high tumor grade (p = 0.0465), and low expression level and advanced pT (p = < 0.0001). It is concluded that clear-cut alterations of β-Catenin expression such as a nuclear and cytoplasmic translocation and a complete expression loss occur rarely in urothelial carcinomas of the urinary bladder. Patients with nuclear expression of β-Catenin in their tumors might benefit from specific therapies once Wnt pathway inhibitors should become safe and efficient.