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β-连环蛋白表达和紧密连接蛋白表达模式作为前列腺癌进展的预后因素。

beta-catenin expression and claudin expression pattern as prognostic factors of prostatic cancer progression.

机构信息

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

出版信息

BJU Int. 2010 Mar;105(5):716-22. doi: 10.1111/j.1464-410X.2009.08808.x. Epub 2009 Oct 10.

Abstract

OBJECTIVE

To investigate the patterns of expression of the junctional proteins beta-catenin and claudins in different prognostic groups of patients with prostatic cancer, to determine their value as prognostic markers.

PATIENTS AND METHODS

We evaluated the samples of 30 patients who had a radical prostatectomy for organ-confined cancer (pT2N0M0), men with clinically advanced cancer, and a control group with benign prostatic hyperplasia. Using immunohistochemistry applied to tissue microarrays, each group was evaluated for claudin-1, -2, -3, -4, -5, -7, -8 and -10, and beta-catenin expression.

RESULTS

There were differences among the three groups in the expression of claudin-1 (P = 0.001), -2 (P = 0.014), -3 (P = 0.027), -4 (P = 0.001), -8 (P = 0.001) and beta-catenin (P = 0.002), regardless of Gleason score. By contrast, claudin-5, -7 and -10 patterns were not significantly different among the groups. Furthermore, claudin-1 (P = 0.014) and -4 (P = 0.004) could be used to distinguish between those patients who had metastases and those who did not.

CONCLUSIONS

The pattern of claudin expression could be a novel diagnostic marker in re-classifying adenocarcinomas, and an additional sensitive predictive factor for a clinically poor prognosis. Our results suggest that patients with organ-confined and advanced cancer are subsets with distinct claudin expression profiles, and that claudin-4 is related to cellular differentiation in prostate cancer, which is not only the receptor molecule for the Clostridium perfringens enterotoxin, and thus a theoretical future therapeutic target for prostate cancer, but also a marker of progression.

摘要

目的

研究连接蛋白β-连环蛋白和紧密连接蛋白在不同前列腺癌预后组中的表达模式,确定其作为预后标志物的价值。

方法

我们评估了 30 例接受根治性前列腺切除术的局限性前列腺癌(pT2N0M0)患者、临床晚期癌症患者和良性前列腺增生对照组患者的样本。使用免疫组织化学应用于组织微阵列,评估每组 claudin-1、-2、-3、-4、-5、-7、-8 和 -10 以及β-连环蛋白的表达。

结果

三组 claudin-1(P=0.001)、-2(P=0.014)、-3(P=0.027)、-4(P=0.001)、-8(P=0.001)和β-连环蛋白(P=0.002)的表达存在差异,而与 Gleason 评分无关。相比之下,claudin-5、-7 和 -10 的模式在各组之间没有显著差异。此外,claudin-1(P=0.014)和-4(P=0.004)可用于区分转移和未转移的患者。

结论

claudin 表达模式可能是重新分类腺癌的新的诊断标志物,也是临床预后不良的另一个敏感预测因子。我们的结果表明,局限性和晚期癌症患者是具有不同 claudin 表达谱的亚组,claudin-4 与前列腺癌的细胞分化有关,它不仅是产气荚膜梭菌肠毒素的受体分子,因此是前列腺癌的一个理论未来治疗靶点,也是进展的标志物。

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