Division of Experimental Cancer Research, Department of Laboratory Medicine in Malmö, Lund University, Clinical Research Center, 205 02, Malmö, Sweden. Tel: +46 40391106,
Anticancer Res. 2013 Dec;33(12):5235-42.
Invasive urothelial carcinoma of the bladder (UCB) is characterized by alterations in cell-cycle regulatory pathways. Defects in the expression of cyclin D1, a key cell-cycle regulator, have been implicated in progression of various types of cancer. In the present study, we investigated whether cyclin D1 expression is associated with clinicopathological parameters and whether it has any potential prognostic value in determining risk of UCB recurrence.
Tissue microarrays containing bladder cancer specimens (n=212) and adjacent normal bladder tissues (n=131) were immunostained using an antibody against cyclin D1. The association between cyclin D1 and clinicopathological parameters including stage, lymph node metastasis, and disease-free survival, were evaluated. Cyclin D1 mRNA expression data from human normal bladder (n=14) and cancer specimens (n=28) were extracted from the public Oncomine database.
Cyclin D1 mRNA and protein expression were significantly higher in UCB compared to adjacent non-malignant bladder tissue (for mRNA p=0.003, for protein p=0.001). Cyclin D1 protein expression was significantly higher in non-invasive tumors than in muscle-invasive UCB (p=0.016). Among patients with muscle-invasive UCB, increased cyclin D1 expression in tumor cells significantly correlated with lymph node metastasis (p<0.001), and there was a trend of cyclin D1 together with lymph node positivity to be associated with disease recurrence (p=0.678). Loss of nuclear cyclin D1 expression in tumor cells was likewise significantly associated with the presence of lymph node metastasis (p<0.001).
Altered expression of cyclin D1 is associated with lymph node metastasis and risk of UCB recurrence. Cyclin D1 expression may therefore have clinical value as a prognostic marker and potential therapeutic target.
膀胱浸润性尿路上皮癌（UCB）的特征是细胞周期调控途径的改变。细胞周期调节因子 cyclin D1 的表达缺陷与各种类型癌症的进展有关。在本研究中，我们研究了 cyclin D1 表达是否与临床病理参数相关，以及它是否具有预测 UCB 复发风险的潜在预后价值。
使用针对 cyclin D1 的抗体对包含膀胱癌标本（n=212）和相邻正常膀胱组织（n=131）的组织微阵列进行免疫染色。评估 cyclin D1 与包括分期、淋巴结转移和无病生存率在内的临床病理参数之间的关系。从公共 Oncomine 数据库中提取了来自人正常膀胱（n=14）和癌症标本（n=28）的 cyclin D1 mRNA 表达数据。
与相邻非恶性膀胱组织相比，UCB 中 cyclin D1 mRNA 和蛋白表达显著升高（mRNA 表达：p=0.003，蛋白表达：p=0.001）。非浸润性肿瘤中的 cyclin D1 蛋白表达明显高于肌肉浸润性 UCB（p=0.016）。在肌肉浸润性 UCB 患者中，肿瘤细胞中 cyclin D1 表达增加与淋巴结转移显著相关（p<0.001），并且 cyclin D1 与淋巴结阳性表达存在趋势与疾病复发相关（p=0.678）。肿瘤细胞中核 cyclin D1 表达缺失同样与淋巴结转移显著相关（p<0.001）。
cyclin D1 的表达改变与淋巴结转移和 UCB 复发风险相关。因此，cyclin D1 表达可能具有作为预后标志物和潜在治疗靶点的临床价值。
