Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
BJU Int. 2010 Mar;105(5):716-22. doi: 10.1111/j.1464-410X.2009.08808.x. Epub 2009 Oct 10.
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.
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.
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.
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.
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。
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。
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。
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。