Nuclear beta-catenin as a marker of outcome in localized prostate cancer

Abstract

9570 Background: Beta-catenin, in its role as a nuclear signaling molecule, has been implicated in prostate carcinogenesis through modulation of androgen receptor activity. Mice in whom beta-catenin is overexpressed in the nuclei of prostatic epithelium develop hyperplastic and dysplastic lesions. Hence this study focused on nuclear beta-catenin expression and aimed to define the pattern of beta-catenin protein expression in the nuclei of normal, hyperplastic and malignant human prostate tissue and to determine whether changes in expression were associated with disease progression and/or prognosis. Methods: Five normal prostates, 26 benign prostatic hypertrophy specimens, 232 radical prostatectomy specimens from patients with clinically localized prostate cancer (PC), 186 specimens of hyperplasia adjacent to PC and 20 cases of advanced PC were assessed for beta-catenin expression using immunohistochemistry. Results: There were significantly lower levels of nuclear beta-catenin expression in localized PC compared to benign prostate tissue (p<0.001). Nuclear beta-catenin expression was also lower in advanced compared to localized PC (p<0.001). In addition, lower levels of nuclear beta-catenin expression (immunoreactivity in <10% of malignant cells) predicted for a shorter biochemical relapse-free survival in patients with localized PC (HR 1.9, 95%CI 1.2–3.0; p=0.008) and were inversely correlated with pre-operative prostate-specific antigen (PSA) levels (p=0.01). Analysis of a low-risk subgroup of patients with pre-operative PSA levels <10 ng/ml (n=114), demonstrated that lower levels of nuclear beta-catenin (<10% of malignant cells) again predicted for a poorer prognosis (HR 3.2, 95%CI 1.4–7.3; p=0.006). Conclusions: Lower levels of nuclear beta-catenin expression are found in malignant compared to benign prostate tissue. Lower nuclear beta-catenin expression is also associated with a poorer prognosis in localized PC, in particular in the low-risk subgroup of patients with pre-operative PSA levels <10 ng/ml. Consequently, nuclear beta-catenin expression may be of clinical utility as a pre-operative prognostic marker in patients with low-risk PC. No significant financial relationships to disclose.