Characterization of Desmoglein Expression in the Normal Prostatic Gland. Desmoglein 2 Is an Independent Prognostic Factor for Aggressive Prostate Cancer

PurposeThe expression of desmogleins (DSGs), which are known to be crucial for establishing and maintaining the cell-cell adhesion required for tissue integrity, has been well characterized in the epidermis and hair follicle; however, their expression in other epithelial tissues such as prostate is poorly understood. Although downregulation of classical cadherins, such as E-cadherin, has been described in prostate cancer tissue samples, the expression of desmogleins has only been previously reported in prostate cancer cell lines. In this study we characterized desmoglein expression in normal prostate tissues, and further investigated whether Desmoglein 2 (DSG2) expression specifically can serve as a potential clinical prognostic factor for patients diagnosed with primary prostate cancer.Experimental DesignWe utilized immunofluorescence to examine DSG2 expression in normal prostate (n = 50) and in a clinically well-characterized cohort of prostate cancer patients (n = 414). Correlation of DSG2 expression with clinico-pathological characteristics and biochemical recurrence was analyzed to assess its clinical significance.ResultsThese studies revealed that DSG2 and DSG4 were specifically expressed in prostatic luminal cells, whereas basal cells lack their expression. In contrast, DSG1 and DSG3 were not expressed in normal prostate epithelium. Further analyses of DSG2 expression in prostate cancer revealed that reduced levels of this biomarker were a significant independent marker of poor clinical outcome.ConclusionHere we report for the first time that a low DSG2 expression phenotype is a useful prognostic biomarker of tumor aggressiveness and may serve as an aid in identifying patients with clinically significant prostate cancer.研究目的：桥粒芯糖蛋白（desmogleins，DSGs）是建立并维持组织完整性所需细胞间黏附的关键蛋白，其在表皮与毛囊中的表达已得到充分表征，但在前列腺等其他上皮组织中的表达情况却鲜有报道。尽管已有研究在前列腺癌组织样本中发现经典钙黏蛋白（如E-钙黏蛋白，E-cadherin）的下调现象，但此前仅在前列腺癌细胞系中报道过桥粒芯糖蛋白的表达。本研究旨在表征正常前列腺组织中的桥粒芯糖蛋白表达谱，并进一步探究桥粒芯糖蛋白2（Desmoglein 2，DSG2）的表达能否作为原发性前列腺癌患者的潜在临床预后因子。 实验设计：本研究采用免疫荧光（immunofluorescence）技术，检测正常前列腺组织（n=50）及一组临床特征明确的前列腺癌患者队列（n=414）中DSG2的表达水平。通过分析DSG2表达与临床病理特征及生化复发的相关性，评估其临床意义。 结果：本研究发现，DSG2与DSG4特异性表达于前列腺腔上皮细胞，而基底细胞不表达这两种蛋白。与之相反，DSG1与DSG3在正常前列腺上皮中无表达。进一步分析前列腺癌组织中的DSG2表达情况可见，该生物标志物的低水平表达是临床不良结局的显著独立预测因子。 结论：本研究首次报道，低DSG2表达表型可作为肿瘤侵袭性的有效预后生物标志物，或可用于辅助甄别具有临床意义的前列腺癌患者。