Sasaki Kazunari, Margonis Georgios A, Wilson Ana, Kim Yuhree, Buettner Stefan, Andreatos Nikolaos, Gani Faiz, Amini Neda, Spolverato Gaya, Pawlik Timothy M
Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
Ann Surg Oncol. 2016 Oct;23(11):3736-3743. doi: 10.1245/s10434-016-5361-6. Epub 2016 Jun 28.
Right-sided and left-sided colorectal cancer (CRC) is known to differ in their molecular carcinogenic pathways. We sought to investigate the variable prognostic implication of KRAS mutation after hepatectomy for colorectal liver metastases (CRLM) according to the site of primary CRC.
A total of 426 patients who underwent a curative-intent hepatic resection and whose KRAS status was available were identified. Clinicopathologic characteristics and long-term outcomes were stratified by KRAS status (wild type vs. mutant type) and primary tumor location (right-sided vs. left-sided). Cecum, right and transverse colon were defined as right-sided, whereas left colon and rectum were defined as left-sided.
Among patients with a right-sided CRC, 5-year recurrence-free survival (RFS) and overall survival (OS) were not correlated with KRAS status (wild type: 30.8 and 47.2 % vs. mutant type: 38.5 and 49.1 %, respectively) (both P > 0.05). Specifically, mutant-type KRAS was not associated with either RFS or OS on multivariable analysis (hazard ratio [HR] 1.51, 95 % confidence interval [CI] 0.73-3.14, P = 0.23 and HR 1.03, 95 % CI 0.51-2.08, P = 0.95, respectively). In contrast, among patients who underwent resection of CRLM from a left-sided primary CRC, 5-year RFS and OS were worse among patients with mutant-type KRAS (wild type: 23.7 and 57.2 % vs. mutant type: 19.6 and 38.2 %, respectively) (both P < 0.05). On multivariable analysis, mutant-type KRAS remained independently associated with worse RFS and OS among patients with a left-sided primary CRC (HR 1.57, 95 % CI 1.01-2.44, P = 0.04 and HR 1.81, 95 % CI 1.11-2.96, P = 0.02, respectively).
KRAS status has a variable prognostic impact after hepatic resection for CRLM depending on the site of the primary CRC. Future studies examining the impact of KRAS status on prognosis after hepatectomy should take into account the primary CRC tumor site.
已知右侧和左侧结直肠癌（CRC）的分子致癌途径有所不同。我们试图根据原发性结直肠癌的部位，研究肝切除术后KRAS突变对结直肠癌肝转移（CRLM）患者预后的不同影响。
共纳入426例行根治性肝切除且可获取KRAS状态的患者。根据KRAS状态（野生型与突变型）和原发性肿瘤位置（右侧与左侧）对临床病理特征和长期预后进行分层。盲肠、右半结肠和横结肠定义为右侧，而左半结肠和直肠定义为左侧。
在右侧结直肠癌患者中，5年无复发生存率（RFS）和总生存率（OS）与KRAS状态无关（野生型：分别为30.8%和47.2%，突变型：分别为38.5%和49.1%）（P均>0.05）。具体而言，在多变量分析中，突变型KRAS与RFS或OS均无关联（风险比[HR]1.51，95%置信区间[CI]0.73 - 3.14，P = 0.23；HR 1.03，95%CI 0.51 - 2.08，P = 0.95）。相比之下，在接受左侧原发性结直肠癌CRLM切除的患者中，突变型KRAS患者的5年RFS和OS较差（野生型：分别为23.7%和57.2%，突变型：分别为19.6%和38.2%）（P均<0.05）。在多变量分析中，突变型KRAS在左侧原发性结直肠癌患者中仍独立与较差的RFS和OS相关（HR 1.57，95%CI 1.01 - 2.44，P = 0.04；HR 1.81，95%CI 1.1 – 2.96，P = 0.02）。
KRAS状态对CRLM肝切除术后的预后影响因原发性结直肠癌的部位而异。未来研究KRAS状态对肝切除术后预后的影响时应考虑原发性结直肠癌的肿瘤部位。
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