Molecular Subtypes Are Frequently Discordant Between Lesions in Patients With Synchronous Colorectal Cancer: Molecular Analysis of 59 Patients

Molecular Subtypes Are Frequently Discordant Between Lesions in Patients With Synchronous Colorectal Cancer: Molecular Analysis of 59 Patients
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DOI:
10.21873/anticanres.13258
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发表时间:
2019-03-01
影响因子:
2
通讯作者:
Ishihara, Soichiro
Ishihara, Soichiro
中科院分区:
医学4区
文献类型:
--
作者:
Arakawa, Keiichi;Hata, Keisuke;Ishihara, Soichiro

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背景:我们的目的是研究同步性结直肠癌(CRC)的分子特征。材料与方法:回顾性分析1,262例结直肠癌患者中59例同时性结直肠癌患者的130个病灶。评价了微卫星、v-Ki-Ras 2 Kristen大鼠肉瘤病毒癌基因同源物(KRAS)、v-raf小鼠肉瘤病毒癌基因同源物B1(BRAF)、肿瘤蛋白53(TP 53)和β-连环蛋白状态,并比较了每例患者同步CRC病变之间的情况。结果:不稳定性亚型、BRAF和β-catenin亚型的表达水平较低,但有统计学意义。KRAS和TP 53不一致的患者在同一患者的病变之间不一致,微卫星KRAS/BRAF亚型的一致性占同步CRC患者的50.8%。在同时性结直肠癌患者中,同时含有mutL同源物1(MLH 1)甲基化和微卫星稳定状态的患者比例为66.7%,至少有一个病变具有高度微卫星不稳定性。结论:目前的研究表明,在同一患者的病变之间的分子亚型的一致性较低。转移性结直肠癌的分子靶向治疗需要对转移性病灶进行分子分析。
Background: We aimed to investigate the molecular features of synchronous colorectal cancer (CRC). Materials and Methods: Out of 1,262 patients with CRC, 130 lesions in 59 patients with synchronous CRC were retrospectively analyzed. Microsatellite, v-Ki-Ras2 Kristen rat sarcoma viral oncogene homolog (KRAS), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), tumor protein 53 (TP53) and beta-catenin status were evaluated and compared between synchronous CRC lesions in each patient. Results: The subtypes of instability, BRAF and beta-catenin subtypes was significant but low. Patients with discordant KRAS and TP53 were not concordant between lesions in the same patient, and concordance of microsatellite KRAS/BRAF subtypes comprised 50.8% of those with synchronous CRC. The rate of patients with lesions containing both mutL homolog 1 (MLH1) methylation and microsatellite stable status was 66.7% in those with synchronous CRC, with at least one lesion with high microsatellite instability. Conclusion: The present study on synchronous CRC demonstrated a low concordance of molecular subtypes between lesions in the same patient. A molecular analysis of metastatic lesions is warranted for molecular targeted therapy of metastatic synchronous CRC.