Molecular Typing and Clinical Characteristics of Synchronous Multiple Primary Colorectal Cancer.
Molecular Typing and Clinical Characteristics of Synchronous Multiple Primary Colorectal Cancer.
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DOI：
10.1001/jamanetworkopen.2022.43457
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发表时间：
2022-11-01
影响因子：
13.8
通讯作者：
Huang, Jun
中科院分区：
文献类型：
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作者：
Zhao, Yandong;Wu, Jingjing;Pei, Fengyun;Zhang, Yanxiang;Bai, Shaomei;Shi, Lishuo;Zhang, Xiang;Ma, Jingjiao;Zhao, Ximeng;Ma, Tonghui;Wang, Jianping;Huang, Meijin;Fan, Xinjuan;Huang, Jun
同步多发原发结直肠癌（sMPCC）的分子特征和临床特点是什么？这项对239例sMPCC患者的队列研究发现，sMPCC患者的错配修复缺陷(dMMR)/微卫星不稳定-高（MSI-H）频率显著高于单一原发性结直肠癌患者。sMPCC各病变的MMR/MSI状态可能不同，可分为3个亚组：全dMMR/MSI- h、dMMR/MSI- h和熟练MMR (pMMR)/微卫星稳定性（MSS）、全pMMR/MSS。这些发现表明，sMPCC可以根据每个病变的MMR/MSI状态划分为亚组，这可能用于指导个性化治疗以更好地进行疾病管理。本队列研究评估同步多发原发结直肠癌的分子特征和临床特征。同步多发原发结直肠癌（sMPCC）在临床上罕见，但其发病率在过去十年中有所增加。然而，sMPCC的分子和临床特征尚不清楚，可能与单一原发性结直肠癌（SPCRC）不同。目的：探讨sMPCC的临床特点、病理变化及分子分型。2012年11月至2021年4月，在中山大学附属第六医院接受治疗的结直肠癌（CRC）患者被纳入本队列研究。随访于2022年1月31日结束。主要结果是使用免疫组化（IHC）检查所有患者中每个病变的错配修复（MMR）状态。计算了微卫星不稳定性（MSI）和肿瘤突变负荷（TMB）。共纳入13276例结直肠癌患者，对239例有临床资料的sMPCC患者（平均[SD]年龄63.3[12.2]岁，173例男性[72.4%]）进行评估。78名sMPCC患者和94名SPCRC患者也接受了基于下一代测序（NGS）的分子检测。sMPCC的MMR (dMMR)/MSI-H缺陷频率显著高于SPCRC，这在IHC（239例患者中有50例对13 037例患者中有872例）和NGS（78例患者中有17例对94例患者中有5例）中得到证实。根据sMPCC患者不同病变的MMR/MSI状态，进一步分为全dMMR/MSI- h、dMMR/MSI- h及熟练MMR (pMMR)/微卫星稳定性（MSS）、全pMMR/MSS 3个亚组。EGFR和PIK3CA变异体在sMPCC患者中更为常见，而TP53变异体在SPCRC患者中较少见。此外，与SPCRC患者相比，sMPCC患者较高的肿瘤突变负担与较高的MSI相关。在这项sMPCC的队列研究中，sMPCC患者的dMMR/MSI-H发生率明显高于SPCRC患者。这些结果提示，sMPCC可根据每个病变的MMR/MSI状态分为3个亚组，可用于指导个性化治疗，更好地进行疾病管理。
What are the molecular characteristics and clinical features of synchronous multiple primary colorectal cancer (sMPCC)? This cohort study of 239 patients with sMPCC found that the deficient mismatch repair (dMMR)/microsatellite instability–high (MSI-H) frequencies in sMPCC were significantly higher than those in single primary colorectal cancer. The MMR/MSI status of each lesion might be different in sMPCC and can be classified into 3 subgroups: all dMMR/MSI-H, dMMR/MSI-H and proficient MMR (pMMR)/microsatellite stability (MSS), and all pMMR/MSS. These findings suggest that sMPCC can be classified into subgroups according to the MMR/MSI status of each lesion, which might be applied to guide personalized therapies for better disease management. This cohort study evaluates the molecular characteristics and clinical features of synchronous multiple primary colorectal cancer. Synchronous multiple primary colorectal cancer (sMPCC) is clinically rare, but its incidence has increased over the past decade. However, little is known about the molecular and clinical features of sMPCC, which may differ from those of single primary colorectal cancer (SPCRC). To evaluate the clinical characteristics and pathogenic variations in lesions and the molecular typing of sMPCC. From November 2012 to April 2021, patients with colorectal cancer (CRC) treated at the Sixth Affiliated Hospital of Sun Yat-sen University were enrolled in this cohort study. Follow-up ended on January 31, 2022. The primary outcome was mismatch repair (MMR) status of each lesion in all patients examined using immunohistochemistry (IHC). Microsatellite instability (MSI) and tumor mutation burden (TMB) were also calculated. A total of 13 276 patients with CRC were enrolled, and 239 patients with sMPCC (mean [SD] age, 63.3 [12.2] years; 173 men [72.4%]) with available clinical data were evaluated. Seventy-eight patients with sMPCC and 94 with SPCRC also underwent next-generation sequencing (NGS)–based molecular testing. The deficient MMR (dMMR)/MSI-H frequencies in sMPCC were significantly higher than those in SPCRC, which was confirmed by both IHC (50 of 239 patients vs 872 of 13 037 patients) and NGS (17 of 78 patients vs 5 of 94 patients). According to the MMR/MSI status of different lesions in patients with sMPCC, they were further divided into 3 subgroups: all dMMR/MSI-H, dMMR/MSI-H and proficient MMR (pMMR)/microsatellite stability (MSS), and all pMMR/MSS. The EGFR and PIK3CA variants were more common, whereas TP53 variants were less prevalent in patients with sMPCC than in those with SPCRC. Moreover, higher tumor mutation burden was associated with higher MSI in patients with sMPCC rather than in those with SPCRC. In this cohort study of sMPCC, the incidence of dMMR/MSI-H in patients with sMPCC was significantly higher than that in patients with SPCRC. These findings suggest that sMPCC can be classified into 3 subgroups according to the MMR/MSI status of each lesion, which might be applied to guide personalized therapies for better disease management.
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影响因子：
12.3
作者：
McLaren W;Gil L;Hunt SE;Riat HS;Ritchie GR;Thormann A;Flicek P;Cunningham F
通讯作者：
Cunningham F
癌症基因组地图集中的致癌信号通路。
影响因子：
64.5
作者：
Sanchez-Vega F;Mina M;Armenia J;Chatila WK;Luna A;La KC;Dimitriadoy S;Liu DL;Kantheti HS;Saghafinia S;Chakravarty D;Daian F;Gao Q;Bailey MH;Liang WW;Foltz SM;Shmulevich I;Ding L;Heins Z;Ochoa A;Gross B;Gao J;Zhang H;Kundra R;Kandoth C;Bahceci I;Dervishi L;Dogrusoz U;Zhou W;Shen H;Laird PW;Way GP;Greene CS;Liang H;Xiao Y;Wang C;Iavarone A;Berger AH;Bivona TG;Lazar AJ;Hammer GD;Giordano T;Kwong LN;McArthur G;Huang C;Tward AD;Frederick MJ;McCormick F;Meyerson M;Cancer Genome Atlas Research Network;Van Allen EM;Cherniack AD;Ciriello G;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
6.1
作者：
Xia C;Dong X;Li H;Cao M;Sun D;He S;Yang F;Yan X;Zhang S;Li N;Chen W
通讯作者：
Chen W
影响因子：
3.2
作者：
Kato T;Alonso S;Muto Y;Noda H;Miyakura Y;Suzuki K;Tsujinaka S;Saito M;Perucho M;Rikiyama T
通讯作者：
Rikiyama T
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
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