Lower levels of nuclear β‐catenin predict for a poorer prognosis in localized prostate cancer

• Published in: International journal of cancer 2005-01, Vol.113 (3), p.415-422
• Main Authors: Horvath, Lisa G., Henshall, Susan M., Lee, C.‐Soon, Kench, James G., Golovsky, David, Brenner, Phillip C., O'Neill, Gordon F., Kooner, Raji, Stricker, Phillip D., Grygiel, John J., Sutherland, Robert L.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; beta Catenin; Biological and medical sciences; Cadherins - metabolism; Case-Control Studies; Cell Nucleus - metabolism; Cytoskeletal Proteins - metabolism; Humans; Immunoenzyme Techniques; Male; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - metabolism; Neoplasm Recurrence, Local - pathology; Neoplasm Recurrence, Local - surgery; Predictive Value of Tests; Prognosis; prognostic marker; Prostate - metabolism; Prostate - pathology; prostate cancer; Prostate-Specific Antigen - metabolism; Prostatectomy; Prostatic Hyperplasia - metabolism; Prostatic Hyperplasia - pathology; Prostatic Hyperplasia - surgery; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Prostatic Neoplasms - surgery; radical prostatectomy; Risk Factors; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the genital tract and mammary gland; Survival Rate; Trans-Activators - metabolism; Tumors; β‐catenin
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.20599

β‐catenin in its role as a nuclear signaling molecule has been implicated in prostate carcinogenesis primarily through modulation of androgen receptor activity. We defined the pattern of β‐catenin protein expression in the nuclei of normal, hyperplastic and malignant human prostate tissue and determined whether differences in expression were associated with disease progression and prognosis. Five normal prostates, 26 benign prostatic hypertrophy specimens, 232 radical prostatectomy specimens from patients with clinically localized prostate cancer (PC) and 20 cases of advanced PC were assessed for β‐catenin expression using immunohistochemistry. Nuclear β‐catenin expression in localized PC was significantly lower than that in benign prostate tissue (p < 0.001) and significantly higher than that in advanced PC tissue (p < 0.001). In addition, lower levels of nuclear β‐catenin expression (< 10% of cancer cells) predicted for a shorter biochemical relapse‐free survival in patients with localized PC (p = 0.008) and were inversely correlated with preoperative prostate‐specific antigen (PSA) levels (p = 0.01). Analysis of the low‐risk subgroup of patients with preoperative PSA levels < 10 ng/ml demonstrated that lower levels of nuclear β‐catenin expression (< 10% of cancer cells) again predicted for a poorer prognosis (p = 0.006). In conclusion, lower levels of nuclear β‐catenin expression are found in malignant compared to benign prostate tissue. In addition, lower nuclear β‐catenin expression is associated with a poorer prognosis in localized PC, in particular, in the low‐risk subgroup of patients with preoperative PSA levels < 10 ng/ml. Thus, the level of nuclear β‐catenin expression may be of clinical utility as a preoperative prognostic marker in low‐risk localized PC.