Lower levels of nuclear β-catenin predict for a poorer prognosis in localized prostate cancer
Lower levels of nuclear β-catenin predict for a poorer prognosis in localized prostate cancer
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DOI：
10.1002/ijc.20599
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发表时间：
2005-01-20
影响因子：
6.4
通讯作者：
Sutherland, RL
中科院分区：
文献类型：
--
作者：
Horvath, LG;Henshall, SM;Sutherland, RL
-连环蛋白作为一种核信号分子，主要通过调节雄激素受体活性参与前列腺癌的发生。我们确定了β -连环蛋白在正常、增生和恶性人类前列腺组织细胞核中的表达模式，并确定表达差异是否与疾病进展和预后相关。应用免疫组织化学方法检测5例正常前列腺、26例良性前列腺肥大、232例根治性前列腺切除术患者及20例晚期前列腺癌患者P-catenin的表达。核β -catenin在局部前列腺癌组织中的表达显著低于前列腺良性组织（P < 0.001），显著高于晚期前列腺癌组织（P < 0.001）。此外，核p -catenin表达水平较低（< 10%的癌细胞）预示着局限性PC患者的生化无复发生存期较短（p = 0.008），并且与术前前列腺特异性抗原（PSA）水平呈负相关（p = 0.01）。对术前PSA水平< 10 ng/ml的低危亚组患者的分析表明，较低水平的核β -连环蛋白表达（< 10%的癌细胞）再次预示较差的预后（p = 0.006）。总之，与良性前列腺组织相比，核β -连环蛋白在恶性前列腺组织中的表达水平较低。此外，较低的核P-catenin表达与局限性PC的预后较差相关，特别是在术前PSA水平< 10 ng/ml的低风险亚组患者中。因此，核β -连环蛋白表达水平可能作为低风险局限性PC的术前预后指标具有临床应用价值。
beta-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 beta-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 P-catenin expression using immunohistochemistry. Nuclear beta-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 P-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 beta-catenin expression (< 10% of cancer cells) again predicted for a poorer prognosis (p = 0.006). In conclusion, lower levels of nuclear beta-catenin expression are found in malignant compared to benign prostate tissue. In addition, lower nuclear P-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 beta-catenin expression may be of clinical utility as a preoperative prognostic marker in low-risk localized PC.