美国微卫星不稳定/错配修复缺陷型结直肠腺癌的流行率和预后。
The Prevalence and Prognosis of Microsatellite Instability-High/Mismatch Repair-Deficient Colorectal Adenocarcinomas in the United States.
机构信息
Harvard Medical School, Boston, MA.
Department of Medicine, Massachusetts General Hospital, Boston, MA.
出版信息
JCO Precis Oncol. 2023 Jan;7:e2200179. doi: 10.1200/PO.22.00179.
PURPOSE
Microsatellite instability (MSI) and DNA mismatch repair (MMR) status is an indispensable biomarker in the management of colorectal cancers. We therefore examined the epidemiology of MSI-high/MMR-deficient colorectal cancers in the United States.
METHODS
Adults presenting with colorectal adenocarcinoma in 2018-2019 were identified from the US National Cancer Database. Attributes associated with MSI-high/MMR-deficiency were identified using multivariable logistic regression and reported using average adjusted probabilities (%) and 99.9% CIs. As a secondary aim, the survival associated with MSI/MMR status was assessed.
RESULTS
Among 101,259 colorectal adenocarcinomas in 2018-2019, 82.0% were microsatellite stable/MMR-proficient, 3.8% MSI-low, and 14.2% MSI-high/MMR-deficient-including 16.6%, 19.9%, 12.4%, and 7.3% of stage I, II, III, and IV cancers, respectively. In locoregional cancers, MSI-high/MMR-deficiency was associated with a bimodal age distribution, female sex, right-sided colonic origin, wild-type , and a prior diagnosis of cancer (all < .001). By race/ethnicity, colorectal adenocarcinomas were MSI-high/MMR-deficient in 16.9% of non-Hispanic White (99.9% CI, 16.5 to 17.4) patients, compared with 11.3% of non-Hispanic Black (99.9% CI, 10.3 to 12.4), 12.4% of Asian/Pacific Islander (99.9% CI, 10.5 to 14.3), and 15.1% of Hispanic (99.9% CI, 13.4 to 16.7) patients (all < .001). Histologically, MSI-high/MMR-deficiency was associated with increasing grade, from 11.3% of well-differentiated tumors (99.9% CI, 10.2 to 12.4) to 28.4% of poorly differentiated cases (99.9% CI, 27.1 to 29.8; < .001). Compared with conventional histology (15.2%, 99.9% CI, 14.8 to 15.6), medullary (41.1%, 99.9% CI, 33.0 to 49.3; < .001) and mucinous (24.6%, 99.9% CI, 22.8 to 26.3; < .001) subtypes-but not signet-ring cell histology (15.5%, 99.9% CI, 11.6 to 19.4; = .79)-were more frequently MSI-high/MMR-deficient when adjusting for clinicopathologic features including grade.
CONCLUSION
Our findings establish the epidemiology, features, and prognostic implications of MSI-high/MMR-deficiency among colorectal adenocarcinoma patients in the United States.
目的
微卫星不稳定性（MSI）和 DNA 错配修复（MMR）状态是结直肠癌管理中不可或缺的生物标志物。因此，我们研究了美国 MSI 高/MMR 缺陷型结直肠癌的流行病学。
方法
从美国国家癌症数据库中确定了 2018-2019 年出现结直肠腺癌的成年人。使用多变量逻辑回归识别与 MSI 高/MMR 缺陷相关的特征，并使用平均调整概率（%）和 99.9%CI 报告。作为次要目标，评估了 MSI/MMR 状态与生存的相关性。
结果
在 2018-2019 年的 101259 例结直肠腺癌中，82.0%为微卫星稳定/MMR 有效，3.8%为 MSI 低，14.2%为 MSI 高/MMR 缺陷，包括 16.6%、19.9%、12.4%和 7.3%的 I 期、II 期、III 期和 IV 期癌症。在局部区域癌症中，MSI 高/MMR 缺陷与双峰年龄分布、女性、右结肠起源、野生型和先前的癌症诊断有关（均<.001）。按种族/族裔划分，非西班牙裔白人患者中有 16.9%的结直肠腺癌为 MSI 高/MMR 缺陷（99.9%CI，16.5 至 17.4），而非西班牙裔黑人患者中有 11.3%（99.9%CI，10.3 至 12.4），亚裔/太平洋岛民患者中有 12.4%（99.9%CI，10.5 至 14.3），西班牙裔患者中有 15.1%（99.9%CI，13.4 至 16.7）（均<.001）。组织学上，MSI 高/MMR 缺陷与肿瘤分级呈正相关，从分化良好的肿瘤（99.9%CI，10.2 至 12.4）的 11.3%增加到分化差的病例（99.9%CI，27.1 至 29.8；<.001）。与常规组织学（15.2%，99.9%CI，14.8 至 15.6）相比，髓样（41.1%，99.9%CI，33.0 至 49.3；<.001）和粘液性（24.6%，99.9%CI，22.8 至 26.3；<.001）亚型更常出现 MSI 高/MMR 缺陷，但在调整包括分级在内的临床病理特征后，印戒细胞组织学（15.5%，99.9%CI，11.6 至 19.4；=0.79）并非如此。
结论
我们的研究结果确立了美国结直肠腺癌患者中 MSI 高/MMR 缺陷的流行病学、特征和预后意义。
Zotero 插件