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BRAF突变在韩国晚期结直肠癌患者中的临床意义。

Clinical meaning of BRAF mutation in Korean patients with advanced colorectal cancer.

作者信息

Kim Bun, Park Soo Jung, Cheon Jae Hee, Kim Tae Il, Kim Won Ho, Hong Sung Pil

机构信息

Bun Kim, Soo Jung Park, Jae Hee Cheon, Tae Il Kim, Won Ho Kim, Sung Pil Hong, Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 120-752, South Korea.

出版信息

World J Gastroenterol. 2014 Apr 21;20(15):4370-6. doi: 10.3748/wjg.v20.i15.4370.

Abstract

AIM

To evaluate the clinicopathological features of colorectal cancer (CRC) with a v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation and its molecular interaction with microsatellite instability (MSI) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) in patients with advanced CRCs.

METHODS

From October 2009 to December 2011, 141 patients with stage III (n = 51) or IV (n = 90) CRCs who were tested for the BRAF mutation at Severance Hospital were included. Among 141 patients, five were excluded due to follow-up loss. Therefore, 136 patients were included in the study. The clinicopathological data, MSI status, and KRAS/BRAF mutation status were reviewed retrospectively. In addition, to evaluating the value of BRAF mutation status, progression-free survival and overall survival in all patients were collected and compared between the BRAF wild-type group and BRAF mutation group.

RESULTS

Of 136 patients, 80 (58.8%) were male and the mean age was 59 years. BRAF and KRAS mutations were detected in 9.6% and 35.3% of patients, respectively. Only 4.3% of patients had MSI-high tumors and there were no MSI-high in tumors with a BRAF mutation. BRAF mutations tended to be more frequent in stage IV than in stage III (11.76% vs 5.88%, P = 0.370). Patients with a BRAF mutation had a lower incidence of KRAS mutation than those without (7.69% vs 38.21%, P = 0.033). Overall survival was significantly shorter in the BRAF mutation group than in the BRAF wild-type group both by univariate analysis (P = 0.041) and multivariate analysis (HR = 2.195; 95%CI: 1.039-4.640; P = 0.039), while progression-free survival was not different according to BRAF mutation status.

CONCLUSION

CRCs with a BRAF mutation have distinct molecular features and resulted in a poor prognosis in Korean patients with advanced CRC.

摘要

目的

评估携带v-Raf鼠肉瘤病毒癌基因同源物B1(BRAF)突变的结直肠癌(CRC)的临床病理特征,及其与晚期结直肠癌患者微卫星不稳定性(MSI)和v-Ki-ras2 Kirsten大鼠肉瘤病毒癌基因同源物(KRAS)的分子相互作用。

方法

纳入2009年10月至2011年12月在Severance医院接受BRAF突变检测的141例III期(n = 51)或IV期(n = 90)结直肠癌患者。141例患者中,5例因失访被排除。因此,136例患者纳入研究。回顾性分析临床病理数据、MSI状态和KRAS/BRAF突变状态。此外,为评估BRAF突变状态的价值,收集所有患者的无进展生存期和总生存期,并在BRAF野生型组和BRAF突变组之间进行比较。

结果

136例患者中,80例(58.8%)为男性,平均年龄59岁。BRAF和KRAS突变分别在9.6%和35.3%的患者中检测到。仅4.3%的患者肿瘤为MSI高,BRAF突变的肿瘤中无MSI高的情况。BRAF突变在IV期比III期更常见(11.76%对5.88%,P = 0.370)。BRAF突变患者的KRAS突变发生率低于未发生BRAF突变的患者(7.69%对38.21%,P = 0.033)。单因素分析(P = 0.041)和多因素分析(HR = 2.195;95%CI:1.039 - 4.640;P = 0.039)均显示,BRAF突变组的总生存期显著短于BRAF野生型组,而无进展生存期根据BRAF突变状态无差异。

结论

携带BRAF突变的结直肠癌具有独特的分子特征,导致韩国晚期结直肠癌患者预后不良。

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