BRAF突变预示着转移性结直肠癌患者行转移灶切除术后预后不良。
BRAF mutation predicts for poor outcomes after metastasectomy in patients with metastatic colorectal cancer.
作者信息
Yaeger Rona, Cercek Andrea, Chou Joanne F, Sylvester Brooke E, Kemeny Nancy E, Hechtman Jaclyn F, Ladanyi Marc, Rosen Neal, Weiser Martin R, Capanu Marinela, Solit David B, D'Angelica Michael I, Vakiani Efsevia, Saltz Leonard B
机构信息
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
出版信息
Cancer. 2014 Aug 1;120(15):2316-24. doi: 10.1002/cncr.28729. Epub 2014 Apr 15.
BACKGROUND
BRAF mutations occur in 5% to 11% of patients with metastatic colorectal cancer (mCRC) and have been associated with poor prognosis. The current study was undertaken to determine the clinicopathologic characteristics, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) mutation frequency, and outcomes after metastasectomy in patients with BRAF-mutant mCRC.
METHODS
Data from 1941 consecutive patients with mCRC who underwent KRAS/BRAF mutation testing between 2009 and 2012 at a single institution were identified to identify BRAF-mutant mCRC cases (92 cases). BRAF wild-type mCRC cases from 2011 (423 cases) served as a control group.
RESULTS
BRAF-mutated mCRC was found to be significantly associated with older age at diagnosis, female sex, right-sided location, poorly differentiated morphology, and mucinous histology compared with wild-type cases. BRAF-mutant cases more frequently progressed from stage III disease (32% vs 17%; P = .003) and among those patients with stage III disease, T4 disease was more common (48% vs 27%; P = .05). PIK3CA was found to be co-mutated in 5% of BRAF-mutant tumors versus 17% of KRAS-mutant tumors (P < .01) and 4% of BRAF/KRAS wild-type cases. Patients with BRAF-mutated mCRC presented more frequently with peritoneal involvement (26% vs 14%; P < 0.01) and less frequently with liver-limited metastases (41% vs 63%; P < .01). Patients with BRAF-mutated mCRC were less likely to undergo metastasectomy (41% vs 26% at 2 years from diagnosis of metastatic disease; P < .01) and were found to have lower overall survival (P < .01) after metastasectomy.
CONCLUSIONS
BRAF-mutant mCRC is associated with worse clinical outcome. Patients with BRAF-mutant tumors more commonly develop peritoneal metastases, less frequently present with disease limited to the liver, and have shorter survival after metastasectomy compared with patients with BRAF wild-type tumors.
背景
BRAF 突变发生于 5%至 11%的转移性结直肠癌（mCRC）患者中，且与预后不良相关。本研究旨在确定 BRAF 突变型 mCRC 患者的临床病理特征、PIK3CA（磷脂酰肌醇-4,5-二磷酸 3-激酶，催化亚基α）突变频率以及转移灶切除术后的结局。
方法
对 1941 例在 2009 年至 2012 年期间于单一机构接受 KRAS/BRAF 突变检测的连续性 mCRC 患者的数据进行分析，以确定 BRAF 突变型 mCRC 病例（92 例）。将 2011 年的 BRAF 野生型 mCRC 病例（423 例）作为对照组。
结果
与野生型病例相比，发现 BRAF 突变型 mCRC 与诊断时年龄较大、女性、右侧部位、低分化形态以及黏液组织学显著相关。BRAF 突变型病例更常从 III 期疾病进展而来（32%对 17%；P = 0.003），并且在那些 III 期疾病患者中，T4 期疾病更为常见（48%对 27%；P = 0.05）。发现 PIK3CA 在 5%的 BRAF 突变型肿瘤中发生共突变，而在 KRAS 突变型肿瘤中为 17%（P < 0.01），在 BRAF/KRAS 野生型病例中为 4%。BRAF 突变型 mCRC 患者更常出现腹膜受累（26%对 14%；P < 0.01），而肝局限性转移较少见（41%对 63%；P < 0.01）。BRAF 突变型 mCRC 患者接受转移灶切除术的可能性较小（从转移性疾病诊断起 2 年时为 41%对 26%；P < 0.01），并且在转移灶切除术后总体生存率较低（P < 0.01）。
结论
BRAF 突变型 mCRC 与更差的临床结局相关。与 BRAF 野生型肿瘤患者相比，BRAF 突变型肿瘤患者更常发生腹膜转移，肝局限性疾病较少见，并且转移灶切除术后生存期较短。
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