Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer.
Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer.
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作者：
Tran B;Kopetz S;Tie J;Gibbs P;Jiang ZQ;Lieu CH;Agarwal A;Maru DM;Sieber O;Desai J
据推测，BRAF突变型癌症代表了转移性结直肠癌（CRC）的一个离散子集，其定义是生存期较差。本研究探讨了BRAF突变型CRC是否以一种独特的转移扩散模式进一步定义，并探讨了BRAF突变和微卫星不稳定性（microsatellite instability， MSI）对转移性CRC预后的影响。利用来自两个主要中心（皇家墨尔本医院和MD安德森癌症中心）的前瞻性临床数据和分子分析，分析了已知BRAF突变状态的患者的临床特征、生存和转移部位。我们确定了524例已知BRAF突变状态的转移性结直肠癌患者，其中57例（11%）为BRAF突变肿瘤。BRAF突变肿瘤与右侧原发肿瘤、MSI和较差生存率显著相关（中位10.4mo vs 34.7mo, p<0.001）。在BRAF突变肿瘤中观察到明显的转移扩散模式，即较高的腹膜转移率（46% v 24%, p=0.001），远处淋巴结转移率（53% v 38%, p=0.008）和较低的肺转移率（35% v 49%, p=0.049）。在另外的生存分析中，与微卫星稳定肿瘤相比，MSI肿瘤的生存期明显较差（22.1个月vs 11.1个月，p=0.017），但这种差异在BRAF突变群体中并不明显。本研究中观察到的转移扩散模式进一步将BRAF突变型CRC定义为一个离散的疾病子集。我们证明，尽管MSI与BRAF突变相关，但在转移性结直肠癌中，MSI不太可能是早期疾病，与较差的生存率相关。
It is hypothesized that BRAF mutant cancers represent a discrete subset of metastatic colorectal cancer (CRC) defined by poorer survival. This study investigates whether BRAF mutant CRC is further defined by a distinct pattern of metastatic spread and explores the impact of BRAF mutation and microsatellite instability (MSI) on prognosis in metastatic CRC. Using prospective clinical data and molecular analyses from two major centers (Royal Melbourne Hospital and MD Anderson Cancer Centre) patients with known BRAF mutation status were analyzed for clinical characteristics, survival and metastatic sites. We identified 524 metastatic CRC patients where BRAF mutation status was known, 57 (11%) were BRAF mutant tumors. BRAF mutant tumors were significantly associated with right-sided primary tumor, MSI and poorer survival (median 10.4mo v 34.7mo, p<0.001). A distinct pattern of metastatic spread was observed in BRAF mutant tumors, namely higher rates of peritoneal metastases (46% v 24%, p=0.001), distant lymph node metastases (53% v 38%, p=0.008) and lower rates of lung metastases (35% v 49%, p=0.049). In additional survival analyses, MSI tumors had significantly poorer survival compared to micro-satellite stable tumors (22.1mo v 11.1 mo, p=0.017), but this difference was not evident in the BRAF mutant population. The pattern of metastatic spread observed in this study further defines BRAF mutant CRC as a discrete disease subset. We demonstrate that, unlikely early stage disease, MSI is associated with poorer survival in metastatic CRC, although this is driven by its association with BRAF mutation.
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影响因子：
11.2
作者：
Samowitz, WS;Sweeney, C;Slattery, ML
通讯作者：
Slattery, ML
影响因子：
8.8
作者：
Catalano, V.;Loupakis, F.;Graziano, F.;Torresi, U.;Bisonni, R.;Mari, D.;Fornaro, L.;Baldelli, A. M.;Giordani, P.;Rossi, D.;Alessandroni, P.;Giustini, L.;Silva, R. R.;Falcone, A.;D'Emidio, S.;Fedeli, S. L.
通讯作者：
Fedeli, S. L.
影响因子：
45.3
作者：
Kopetz, Scott;Chang, George J.;McWilliams, Robert R.
通讯作者：
McWilliams, Robert R.
影响因子：
2.8
作者：
Mueller, C. I.;Schulmann, K.;Graeven, U.
通讯作者：
Graeven, U.
影响因子：
24.5
作者：
Ogino S;Nosho K;Kirkner GJ;Kawasaki T;Meyerhardt JA;Loda M;Giovannucci EL;Fuchs CS
通讯作者：
Fuchs CS