Up-regulation of Wnt-1 and β-catenin production in patients with advanced metastatic prostate carcinoma -: Potential pathogenetic and prognostic implications

Up-regulation of Wnt-1 and β-catenin production in patients with advanced metastatic prostate carcinoma -: Potential pathogenetic and prognostic implications
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DOI:
10.1002/cncr.20518
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发表时间:
2004-09-15
期刊:
影响因子:
6.2
通讯作者:
Rabbani, SA
Rabbani, SA
中科院分区:
医学1区
文献类型:
--
作者:
Chen, GP;Shukeir, N;Rabbani, SA

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背景资料。WNT-1和β-连环蛋白的表达水平在多种恶性肿瘤中起重要作用。作者测定了正常和恶性前列腺癌细胞系中WNT-1和β-连环蛋白的产生水平。方法采用免疫组织化学方法检测67例前列腺癌患者的前列腺癌细胞株和石蜡包埋标本中WNT-1和β-catenin的表达。并与肿瘤AR表达、淋巴结和骨转移情况进行比较。结果:WNT-1和β-catenin在正常前列腺细胞中低水平表达,而在人前列腺癌细胞系中高表达。WNT-1和胞浆/胞核β-连环蛋白在前列腺癌组织中的表达分别为52%和34%。Wnt-1和β-catenin在77%的淋巴结转移灶和85%的骨转移灶中高表达。这些表达水平的增加与这些患者的Gleason评分和血清PSA水平直接相关。骨转移癌组织中WNT-1和β-连环素的表达水平最高,而正常前列腺组织中未见可检测到的β-连环素的核染色。结论:WNT-1和β-连环素的高水平表达与晚期、转移性、激素不敏感的前列腺癌有关,可作为疾病进展的标志。(C)2004年美国癌症协会。
BACKGROUND. Wnt-1 and beta-catenin expression levels play an important role in several malignancies. The authors determined the level of production of Wnt-1 and beta-catenin in normal and malignant human prostate carcinoma cell lines. Surgical pathology specimens from primary prostatic adenocarcinoma, lymph node metastases, and skeletal metastases were used to establish a correlation between the level of Wnt-1/beta-catenin expression, Gleason score, serum prostate-specific antigen (PSA) status, and androgen receptor (AR) status.METHODS. Immunohistochemical analysis was used to investigate the expression of Wnt-1 and beta-catenin in human prostate carcinoma cell lines and in paraffin embedded sections of archival samples from 67 patients with prostate carcinoma. Comparison was made with the expression of tumoral AR and lymph node and skeletal metastases. These results were used to establish a correlation with the clinicopathologic status of patients with prostate carcinoma.RESULTS. Levels of both Wnt-1 and beta-catenin were low in normal prostate cells and were expressed highly in human prostate carcinoma cell lines. Wnt-1 and cytoplasmic/nuclear beta-catenin expression was observed in 52% and 34%, respectively, of primary prostate carcinoma specimens. High levels of expression of Wnt-1 and beta-catenin were seen in 77% of lymph node metastases and in 85% of skeletal metastases. These increased levels of expression were related directly to the Gleason score and to serum PSA levels in these patients. Maximum levels of Wnt-1 and beta-catenin production were observed in skeletal metastases, whereas normal prostatic tissue failed to exhibit any detectable nuclear staining for beta-catenin.CONCLUSIONS. High levels of Wnt-1 and beta-catenin expression were associated with advanced, metastatic, hormone-refractory prostate carcinoma, in which they can serve as markers of disease progression. (C) 2004 American Cancer Society.