Characterization and Clinical Outcomes of DNA Mismatch Repair-deficient Small Bowel Adenocarcinoma.
Characterization and Clinical Outcomes of DNA Mismatch Repair-deficient Small Bowel Adenocarcinoma.
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DOI：
10.1158/1078-0432.ccr-20-2892
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发表时间：
2021-03-01
期刊：
影响因子：
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通讯作者：
Stadler ZK
中科院分区：
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作者：
Latham A;Shia J;Patel Z;Reidy-Lagunes DL;Segal NH;Yaeger R;Ganesh K;Connell L;Kemeny NE;Kelsen DP;Hechtman JF;Nash GM;Paty PB;Zehir A;Tkachuk KA;Sheikh R;Markowitz AJ;Mandelker D;Offit K;Berger MF;Cercek A;Garcia-Aguilar J;Saltz LB;Weiser MR;Stadler ZK
LS 背景下小肠腺癌 (SBA) 的患病率和临床特征尚未得到充分研究。我们根据 DNA 错配修复和/或微卫星不稳定性 (MMR/MSI) 和种系突变状态来表征 SBA，并比较临床结果。一项单一机构审查确定了 100 个 SBA。通过 MSI 传感器评估肿瘤的 MSI 和/或通过免疫组织化学 (IHC) 染色评估相应的 MMR 蛋白表达。分析种系 DNA 中已知癌症易感基因的突变，包括 MMR（MLH1、MSH2、MSH6、PMS2、EPCAM）。临床变量与 MMR/MSI 状态相关。 26% (26/100; 95% CI: 18.4-35.4) 的 SBA 表现出 MMR 缺陷 (MMR-D)。 LS 总体患病率为 10%，MMR-D SBA 中 LS 患病率为 38.5%。非 LS MMR-D 与 MMR-P 型 SBA 诊断时的中位年龄相似（65 vs 61，p = 0.75），但 LS 中的中位年龄明显年轻（47.5 vs 61；p = 0.03）。 MMR-P 中同步/异时癌症的患病率为 9% (6/67)，而 MMR-D SBA 中同步/异时癌症的患病率为 34.6% (9/26)，其中 LS 中的患病率为 66.7% (6/9) (p=0.0002)。在 MMR-P 组中，52.2% (35/67) 的患者出现转移性疾病，而 MMR-D 组中这一比例为 23.1% (6/26) (p=0.008)。在 MMR-P I/II 期患者中，88.2% (15/17) 复发，而 MMR-D 组复发率为 18.2% (2/11) (p=0.0002)。与 MMR-P SBA 相比，MMR-D SBA 与早期疾病和较低的复发率相关，类似于结直肠癌中的观察结果。 MMR-D SBA 的患病率为 38.5%，因此有必要对 MMR-D SBA 进行种系 LS 检测。
The prevalence and clinical characteristics of small bowel adenocarcinomas (SBAs) in the setting of LS have not been well-studied. We characterized SBA according to DNA mismatch repair and/or microsatellite instability (MMR/MSI) and germline mutation status and compared clinical outcomes. A single-institution review identified 100 SBAs. Tumors were evaluated for MSI via MSIsensor and/or corresponding MMR protein expression via immunohistochemical (IHC) staining. Germline DNA was analyzed for mutations in known cancer-predisposition genes, including MMR (MLH1, MSH2, MSH6, PMS2, EPCAM). Clinical variables were correlated with MMR/MSI status. 26% (26/100; 95% CI: 18.4-35.4) of SBAs exhibited MMR deficiency (MMR-D). LS prevalence was 10% overall and 38.5% among MMR-D SBAs. Median age at SBA diagnosis was similar in non-LS MMR-D vs MMR-proficient (MMR-P) SBAs (65 vs 61, p= 0.75), but significantly younger in LS (47.5 vs 61; p=0.03). The prevalence of synchronous/metachronous cancers was 9% (6/67) in MMR-P vs 34.6% (9/26) in MMR-D SBA, with 66.7% (6/9) of these in LS (p=0.0002). In the MMR-P group, 52.2% (35/67) of patients presented with metastatic disease, compared to 23.1% (6/26) in the MMR-D group (p=0.008). In MMR-P stage I/II patients, 88.2% (15/17) recurred, compared to 18.2% (2/11) in the MMR-D group (p=0.0002). When compared to MMR-P SBA, MMR-D SBA is associated with earlier-stage disease and lower recurrence rates, similar to observations in colorectal cancer. With a 38.5% prevalence in MMR-D SBA, germline LS testing in MMR-D SBA is warranted.