Lipsyc Marla, Yaeger Rona
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
J Gastrointest Oncol. 2015 Dec;6(6):645-9. doi: 10.3978/j.issn.2078-6891.2015.045.
Somatic mutation status in metastatic colorectal cancer (mCRC) is becoming increasingly clinically relevant as it may be correlated not only with response to biologic therapies, but also with site-specific pattern of metastatic spread and outcome. In this review, we describe our current understanding of associations between mutational activation of the KRAS, BRAF, PIK3CA, and NRAS oncogenes and clinical outcomes and metastatic patterns of mCRC. The presence of a KRAS mutation is associated with a distinct pattern of metastatic spread with decreased liver metastases and increased lung, brain, and bone metastases. In patients who undergo resection of colorectal liver metastases (CLM) with curative intent, KRAS mutation is associated increased risk of recurrence, worse survival, and increased recurrence outside of the liver, particularly in the lung, but also in the brain and bone. BRAF mutation, a poor prognostic factor in mCRC, is associated with decreased liver-limited metastasis and increased peritoneal and distant lymph node metastases. PIK3CA mutation does not clearly affect outcomes in the metastatic setting, but is associated with concurrent KRAS mutations, and has been associated with an increased incidence of lung and brain metastases, metastatic sites preferentially involved in KRAS mutant mCRC. NRAS mutation may confer worse survival and early studies suggest NRAS mutation may promote tumorigenesis in the setting of colorectal inflammation. As metastasectomy with curative intent is increasingly considered in patients with mCRC, understanding patterns of metastasis associated with tumor mutations may help focus medical treatment, surgical management, and surveillance in patients with mCRC.
转移性结直肠癌（mCRC）的体细胞突变状态在临床上的相关性日益增加，因为它不仅可能与生物治疗的反应相关，还与转移扩散的部位特异性模式和预后有关。在本综述中，我们描述了目前对KRAS、BRAF、PIK3CA和NRAS癌基因突变激活与mCRC临床结局和转移模式之间关联的理解。KRAS突变的存在与一种独特的转移扩散模式相关，肝转移减少，肺、脑和骨转移增加。在接受根治性切除结直肠肝转移（CLM）的患者中，KRAS突变与复发风险增加、生存较差以及肝外复发增加有关，特别是在肺，也包括脑和骨。BRAF突变是mCRC的不良预后因素，与肝局限性转移减少和腹膜及远处淋巴结转移增加有关。PIK3CA突变在转移情况下对结局没有明显影响，但与KRAS同时突变有关，并且与肺和脑转移的发生率增加有关，这些转移部位在KRAS突变的mCRC中优先受累。NRAS突变可能导致较差的生存，早期研究表明NRAS突变可能在结直肠炎症背景下促进肿瘤发生。由于越来越多的mCRC患者考虑进行根治性转移灶切除术，了解与肿瘤突变相关的转移模式可能有助于聚焦mCRC患者的药物治疗、手术管理和监测。
