FGFR3 mutational status and protein expression in patients with bladder cancer in a Jordanian population
FGFR3 mutational status and protein expression in patients with bladder cancer in a Jordanian population
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DOI：
10.1016/j.canep.2010.05.003
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发表时间：
2010-12-01
影响因子：
2.6
通讯作者：
Haddad, Yazan
中科院分区：
文献类型：
--
作者：
Bodoor, Khaldon;Ghabkari, Abdulhameed;Haddad, Yazan
膀胱癌占约旦所有新诊断癌症的近5%，男性发病率高得多。最近的研究表明，FGFR 3的激活突变是非侵袭性低级别膀胱肿瘤中最常见的发现。在这项研究中，我们回顾性地调查了121例膀胱癌患者的队列，这些患者患有不同级别和阶段的肿瘤，以了解FGFR 3的分子变化。在pTa、pT 1、pT 2和pT 3病例中分别观察到49%、34%、15%和2%的FGFR 3过表达。G1、G2和G3期FGFR 3表达阳性率分别为45%、26%和30%。对FGFR 3外显子7、10和15的突变分析鉴定了4个先前报道的突变，即R248 C（n = 4; 10%）、S249 C（n = 23; 59%）、Y375 C（n = 7; 18%）、G382 R（n = 4; 10%）和1个新突变G382 E（n = 1; 3%）。我们的研究结果表明，FGFR 3的突变和过表达是相关的，并在早期（pTa和pT 1）和低级别（G1和G2）膀胱肿瘤中更普遍。生存分析显示FGFR 3的变化对患者的生存没有贡献。多变量考克斯比例风险模型分析总生存期的以下变量：年龄，性别，肿瘤分期和分级，FGFR 3（表达和突变）显示，年龄，肿瘤分期和分级是膀胱癌患者总生存期的独立预测因子。我们的工作是第一个解决约旦膀胱癌患者中FGFR 3的分子状态，并为FGFR 3作为膀胱肿瘤起始的关键参与者提供进一步支持。(C)2010爱思唯尔有限公司版权所有。
Bladder cancer accounts for nearly 5% of all newly diagnosed cancers in Jordan, with a much higher frequency in males. Recent studies have shown that activating mutations in FGFR3 are the most common findings in non-invasive low grade bladder tumors. In this study, we, retrospectively, investigated a cohort of 121 bladder cancer patients with various grades and stages of the tumor for molecular changes in FGFR3. Overexpression of FGFR3 was observed in 49%, 34%, 15%, and 2% of pTa, pT1, pT2, and pT3 cases, respectively. Further, FGFR3 expression was positive in 45%, 26%, and 30% of G1, G2 and G3 cases, respectively. Mutational analysis of exons 7, 10 and 15 of FGFR3 identified four previously reported mutations, namely R248C (n = 4; 10%), S249C (n = 23; 59%), Y375C (n = 7; 18%), G382R (n = 4:10%), and one novel mutation, G382E (n = 1; 3%). Our results indicate that both mutations and overexpression of FGFR3 are correlated together, and are more prevalent in early stage (pTa and pT1) and low grade (G1 and G2) bladder tumors. Survival analysis showed no contribution of changes in FGFR3 on the patient's survival. Multivariate Cox proportional hazards model analysis of overall survival for the following variables: age, gender, stage and grade of tumor, and FGFR3 (expression and mutation) revealed that age, stage and grade of tumor are independent predictors of overall survival in patients with bladder cancer. Our work is the first to address the molecular status of FGFR3 in Jordanian patients with bladder cancer, and provides further support for FGFR3 as a key player in the initiation of bladder tumors. (C) 2010 Elsevier Ltd. All rights reserved.