Loss of p16 expression and chromosome 9p21 LOH in predicting outcome of patients affected by superficial bladder cancer
Loss of p16 expression and chromosome 9p21 LOH in predicting outcome of patients affected by superficial bladder cancer
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DOI：
10.1016/j.jss.2007.01.012
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发表时间：
2007-12-01
影响因子：
2.2
通讯作者：
Dal Canto, Maurizio
中科院分区：
文献类型：
--
作者：
Bartoletti, Riccardo;Cai, Tommaso;Dal Canto, Maurizio
目标。目的探讨低级别(G1-G2)尿路上皮癌患者外周血中p16基因表达和9p21基因杂合性缺失(LOH)对患者预后的影响。56名被诊断为尿路上皮性膀胱癌的患者参加了这项前瞻性研究。通过聚合酶链式反应分析，对每个患者的血液/肿瘤配对样本进行杂合性缺失分析。对9号染色体上的D9S171(9p21)基因座进行了检测。所有肿瘤均行p16免疫组织化学染色。P16和杂合性缺失分析的数据与随访数据进行比较，以评估这些分子标记物对预后的作用。33例患者(58.9%)p16表达缺失，且与无复发概率的降低显著相关(P<；0.0001)。与分期(P=0.162)或分级(P=0.051)无关。染色体9p21(D9S171)有43例(76.7%)发生杂合性缺失。染色体9p21上p16表达缺失与LOH显著相关(P=0.005)。Kaplan-Meier曲线显示无复发状态与p16表达显著相关(P=0.0001)。经多因素分析，p16表达(P=0.002)和病灶个数(P=0.002)是影响肿瘤复发的独立因素。我们的研究强调了p16在预测低级别尿路上皮性膀胱癌患者无复发概率中的预后作用，并强调了该方法可用于日常泌尿外科临床实践，以更好地描述尿路上皮性膀胱癌的自然病史。(C)2007 Elsevier Inc.保留所有权利。
Objectives. To evaluate the prognostic role of p16 expression and loss of heterozygosity (LOH) on chromosome 9p21 in patients affected by low-grade (G1-G2) urothelial bladder cancer.Methods. Fifty-six consecutive patients with diagnosis of urothelial bladder cancer were enrolled in this prospective study. LOH analysis was performed on a blood/ tumor pair sample of each patient, by using polymerase chain reaction analysis. The D9S171 (9p21) locus on chromosome 9 was investigated. All tumors were stained immunohistochemically for p16. Data from p16 and LOH analyses were compared with follow-up data to evaluate the prognostic role of these molecular markers.Results. Loss of p16 expression was found in 33 patients (58.9%) and was significantly associated with the reduced recurrence-free probability (P < 0.0001). No correlations were reported with stage (P = 0.162) or grade (P = 0.051). Forty-three patients (76.7%) showed LOH on chromosome 9p21 (D9S171). A significant association was observed between loss of p16 expression and LOH on chromosome 9p21 (P = 0.005). The Kaplan-Meier curves showed a significant correlation between recurrence-free status and p16 expression (P = 0.0001). By multivariate analysis, p16 expression (P = 0.002) and number of lesions (P = 0.002) were identified as independent tumor recurrence factors.Conclusions. Our study highlights the prognostic role of p16 in predicting the recurrence-free probability in patients affected by low-grade urothelial bladder and highlights the fact that this method could be used in everyday urologic clinical practice to better characterize the natural history of urothelial bladder carcinomas. (c) 2007 Elsevier Inc. All rights reserved.