Abstract β-Catenin (CTNNB1) alterations are of potential interest as a prognostic feature and an option for therapeutic targeting in cancer. β-Catenin (CTNNB1) is a dual function protein with roles in cell cohesion and gene transcription 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 multiple cancer promoting genes. Aberrant nuclear β-Catenin translocation is especially caused by loss of function mutations of genes encoding proteins of the β-Catenin destruction complex or by gain of function mutations of CTNNB1. Affected cancers can be recognized by immunohistochemistry (IHC) due to their aberrant nuclear/cytoplasmic β-Catenin staining. To study the prevalence and the potential role of aberrant β-Catenin staining patterns, more than 6,000 adenocarcinomas of the prostate were analyzed by immunohistochemistry (IHC) in a tissue microarray format. All patients had been treated by radical prostatectomy. Clinical follow-up data were available for 4,895 patients. Among 6,114 evaluable cancers, membranous β-Catenin staining was considered strong in 2,893 (47.3%), moderate in 2,737 (44.8%), and weak in 326 (5.3%) while additional 158 (2.6%) showed unequivocal nuclear/cytoplasmic translocation of β-Catenin protein. Strong membranous β-Catenin staining was more common in 1,926 tumors with (61.4%) than in 2,617 tumors without (37.7%) TMPRSS2:ERG fusion (p0.0001). Strong membranous β-Catenin staining was significantly associated with advanced pT stage as well as a high traditional (p0.0001) and quantitative Gleason grade (p0.0001). A comparison of β-Catenin staining data with PSA recurrence revealed only minimal differences between tumors with weak, moderate, and strong membranous staining but a significantly increased risk for PSA recurrence for patients with nuclear/cytoplasmic β-Catenin translocation (p=0.0448). A subgroup analysis of 1,258 ERG positive and 1,672 ERG negative cancers revealed that the unfavorable prognostic impact of nuclear/cytoplasmic β-Catenin translocation was only seen in the ERG negative group (p0.0001) while there was even a tendency towards better patient outcome in case of nuclear/cytoplasmic β-Catenin translocation in ERG positive cancers. It is concluded that nuclear/cytoplasmic β-Catenin translocation as detected by IHC is rare in prostate cancer and occurs in about 3% of patients. Only in ERG negative cancers, nuclear/cytoplasmic translocation of β-Catenin is strongly linked to unfavorable disease course. The strong prognostic role of the β-Catenin status could potentially be exploited for clinically relevant disease course prediction. Citation Format: Florian Lutz, Osman Gökalp, Ronald Simon, Hans Heinzer, Alexander Haese, Sarah Minner, Guido Sauter, Thorsten Schlomm, Martina Kluth, Claudia Hube-Magg. Nuclear/cytoplasmic translocation of β-Catenin protein is a strong predictor of unfavorable patient prognosis in ERG negative but not in ERG positive prostate cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7224.
Lutz et al. (Fri,) studied this question.