Predictive and prognostic value of microsatellite instability in patients with advanced colorectal cancer treated with a fluoropyrimidine and oxaliplatin containing first-line chemotherapy.: A report of the AIO Colorectal Study Group

Predictive and prognostic value of microsatellite instability in patients with advanced colorectal cancer treated with a fluoropyrimidine and oxaliplatin containing first-line chemotherapy.: A report of the AIO Colorectal Study Group
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DOI:
10.1007/s00384-008-0504-2
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发表时间:
2008-11-01
影响因子:
2.8
通讯作者:
Graeven, U.
Graeven, U.
中科院分区:
医学3区
文献类型:
--
作者:
Mueller, C. I.;Schulmann, K.;Graeven, U.

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背景与目的微卫星不稳定性(MSI)是结直肠癌(CRC)患者预后的潜在指标。到目前为止,研究其在晚期CRC中的作用的研究数量有限。我们的研究探讨了高MSI(MSI-H)在接受5-FU/奥沙利铂为主的化疗的患者中的价值,最近只有一项进一步的研究完成了这项研究。在这项研究中,我们调查了108例转移性结直肠癌患者的肿瘤组织,这些患者接受了前瞻性随机试验,比较了两种奥沙利铂和5-FU为主的治疗方案(FUFOX和CAPOX),共涉及474名患者。我们确定了高度微卫星不稳定性的发生率和预后价值。样本通过与国家卫生研究所参考小组对应的聚合酶链式反应进行分析。并对错配修复蛋白MLH1、MSH2和MSH6进行免疫组织化学染色。与非MSI-H患者相比,MSI-H患者的疾病控制率较低(p=0.02)。结论MSI-H在转移性结直肠癌中的发生率较低。我们的数据表明,MSI-H可能与5-FU/奥沙利铂治疗反应较差有关。这一发现需要在更大的队列中得到证实。
Background and aims Microsatellite instability (MSI) is a potential indicator of prognosis in patients with colorectal cancer (CRC). To date, there are a limited number of studies which investigated its role in advanced CRC. Our study investigated the value of high degree of MSI (MSI-H) in patients treated with 5-FU/oxaliplatin-based chemotherapy which has been done by only one further study recently.Patients and methods In this study, we investigated tumour tissues from 108 patients with metastatic CRC who were treated in a prospective, randomised trial comparing two oxaliplatin and 5-FU-based therapy regimens (FUFOX vs. CAPOX) involving a total of 474 patients. We determined the incidence and prognostic value of a high degree of microsatellite instability. The specimens were analysed by PCR corresponding to the National Institute of Health reference panel. In addition, immunostaining of the mismatch repair proteins MLH1, MSH2 and MSH6 was performed.Results and findings The incidence of MSI-H was 4%. MSI-H was correlated with a lower rate of disease control compared to non-MSI-H patients (p = 0.02). However, there was no correlation between MSI-H and progression-free survival or overall survival.Interpretation and conclusion MSI-H incidence in metastatic CRC was low. Our data suggest that MSI-H may be correlated with a poorer response to a 5-FU/oxaliplatin treatment. This finding needs confirmation in a larger cohort.