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结直肠癌原发肿瘤与肝转移灶之间KRAS突变状态的不一致性:对根治性切除术后长期生存的影响

Discordance of KRAS Mutational Status between Primary Tumors and Liver Metastases in Colorectal Cancer: Impact on Long-Term Survival Following Radical Resection.

作者信息

Ardito Francesco, Razionale Francesco, Salvatore Lisa, Cenci Tonia, Vellone Maria, Basso Michele, Panettieri Elena, Calegari Maria Alessandra, Tortora Giampaolo, Martini Maurizio, Giuliante Felice

机构信息

Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A, Gemelli IRCCS, 00168 Rome, Italy.

Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.

出版信息

Cancers (Basel). 2021 Apr 29;13(9):2148. doi: 10.3390/cancers13092148.

Abstract

If KRAS mutation status of primary colorectal tumor is representative of corresponding colorectal liver metastases (CRLM) mutational pattern, is controversial. Several studies have reported different rates of KRAS discordance, ranging from 4 to 32%. Aim of this study is to assess the incidence of discordance and its impact on overall survival (OS) in a homogenous group of patients. KRAS mutation status was evaluated in 107 patients resected for both primary colorectal tumor and corresponding CRLM at the same institution, between 2007 and 2018. Discordance rate was 15.9%. Its incidence varied according to the time interval between the two mutation analyses ( = 0.025; Pearson correlation = 0.2) and it was significantly higher during the first 6 months from the time of primary tumor evaluation. On multivariable analysis, type of discordance (wild-type in primary tumor, mutation in CRLM) was the strongest predictor of poor OS ( < 0.001). At multivariable logistic regression analysis, the number of CRLM >3 was an independent risk factor for the risk of KRAS discordance associated with the worst prognosis (OR = 4.600; = 0.047). Results of our study suggested that, in the era of precision medicine, possibility of KRAS discordance should be taken into account within multidisciplinary management of patients with metastatic colorectal cancer.

摘要

原发性结直肠癌肿瘤的KRAS突变状态是否代表相应的结直肠癌肝转移(CRLM)突变模式,存在争议。几项研究报告了不同的KRAS不一致率,范围从4%到32%。本研究的目的是评估一组同质患者中不一致的发生率及其对总生存期(OS)的影响。在2007年至2018年期间,对同一机构中107例因原发性结直肠癌肿瘤和相应CRLM而接受手术切除的患者的KRAS突变状态进行了评估。不一致率为15.9%。其发生率根据两次突变分析之间的时间间隔而有所不同(P = 0.025;Pearson相关性 = 0.2),并且在原发性肿瘤评估后的前6个月内显著更高。在多变量分析中,不一致类型(原发性肿瘤为野生型,CRLM为突变型)是OS较差的最强预测因素(P < 0.001)。在多变量逻辑回归分析中,CRLM数量>3是与最差预后相关的KRAS不一致风险的独立危险因素(OR = 4.600;P = 0.047)。我们的研究结果表明,在精准医学时代,转移性结直肠癌患者的多学科管理中应考虑KRAS不一致的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac17/8125529/e2350b3e895e/cancers-13-02148-g001.jpg

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