Expression of Vitamin D Receptor (VDR) in Urinary Bladder Carcinoma: Immunohistochemical and Histopathological Study

R. Sharaf, Basma Mostafa Mahmoud Abdalla, Samia Ibrahim El Naggar, Wesam I Moustafa
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Abstract

Background: Bladder cancer is the most common malignancy of the urinary tract. Calcitriol [1,25 (OH)2vitamin D3] has anticancer effects mediated through binding to vitamin D receptor (VDR). The expression of VDR is present in many normal and cancer tissues. But, there is little information about its expression in urinary bladder carcinoma. This study aimed to analyze VDR immunohistochemical expression in 74 Egyptian patients with urinary bladder carcinoma and to evaluate its association with different clinicopathological parameters. Methods: Sections from formalin-fixed, paraffin-embedded tumor blocks were stained immunohistochemically using monoclonal anti-VDR antibody. VDR protein expression as well as its immunostaining patterns were recorded and scored separately in each case using semi-quantitative immunoreactive score. Results: VDR was consistently expressed in the included histologically normal urothelium while tumor cells showed variable degrees of expression. Cytoplasmic/membranous VDR expression was common among the studied cases especially those with urothelial morphology (p = 0.076). While, the mean nuclear VDR was significantly (p = 0.007) higher in non-urothelial tumors. Nuclear VDR was significantly associated with muscle invasion (p = 0.000) and tumor stage (p = 0.001) in urothelial carcinoma. It was also statistically related to tumor grade, stage and muscle invasion in non-urothelial tumors (p = 0.002, 0.003 and 0.012, respectively). Conclusion: there was a significant relation between nuclear VDR expression and prognostic markers suggesting its decrease as an indicator of a poorer prognosis. Vitamin D supplementation may represent a new treatment option for patients with bladder cancer.
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维生素D受体(VDR)在膀胱癌组织中的表达:免疫组织化学和组织病理学研究
背景:膀胱癌是泌尿道最常见的恶性肿瘤。骨化三醇[1,25 (OH)2维生素D3]通过与维生素D受体(VDR)结合而具有抗癌作用。VDR的表达存在于许多正常和癌组织中。但是,关于其在膀胱癌中的表达却知之甚少。本研究旨在分析74例埃及膀胱癌患者的VDR免疫组织化学表达,并评估其与不同临床病理参数的关系。方法:用单克隆抗vdr抗体对福尔马林固定、石蜡包埋肿瘤块切片进行免疫组织化学染色。采用半定量免疫反应评分法分别记录各组VDR蛋白表达及免疫染色模式。结果:VDR在病理正常的尿路上皮中表达一致,而肿瘤细胞表达程度不同。细胞质/膜性VDR表达在研究病例中很常见,特别是尿路上皮形态(p = 0.076)。而非尿路上皮肿瘤的平均核VDR显著(p = 0.007)升高。在尿路上皮癌中,核VDR与肌肉侵袭(p = 0.000)和肿瘤分期(p = 0.001)显著相关。非尿路上皮肿瘤与肿瘤分级、分期、肌肉侵袭也有统计学意义(p分别= 0.002、0.003、0.012)。结论:核VDR表达与预后标志物有显著相关性,提示其表达降低是预后较差的指标。补充维生素D可能是膀胱癌患者的一种新的治疗选择。
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