错配修复缺陷肿瘤的分期依赖性预后转变：评估II期和III期结肠癌患者的预后
Stage-dependent prognostic shift in mismatch repair-deficient tumors: Assessing patient outcomes in stage II and III colon cancer.
作者信息
Hestetun Kjersti Elvestad, Rosenlund Nina Benedikte, Stanisavljević Luka, Dahl Olav, Myklebust Mette Pernille
机构信息
Department of Clinical Science, University of Bergen, Bergen, Norway.
Department of Oncology, Haukeland University Hospital, Bergen, Norway.
出版信息
Front Oncol. 2022 Aug 30;12:853545. doi: 10.3389/fonc.2022.853545. eCollection 2022.
INTRODUCTION
Deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H) is associated with an improved prognosis in colon cancer stage II but poor prognosis in stage IV colon cancer. The clinical significance of dMMR in colon cancer stage III is not established.
METHODS
Tissue microarrays (TMAs) from 544 patients with colon cancer stage II and III with clinicopathological and survival data were stained for mismatch repair (MMR) proteins, CD3, CD8, and programmed death ligand-1 (PD-L1), and programmed death ligand- 1 (PD-L1). Patient outcomes were reviewed.
RESULTS
In stage III colon cancer, dMMR was a marker of poor disease-free survival (DFS) (Kaplan-Meier, mean survival in months: dMMR: 28.76 (95% CI 18.46-39.05) vs. pMMR 40.91 (37.20-44.63), p=0.014, multivariate Cox regression: hazard ratio (HR) 4.17 (95% CI 2.02-8.61), p<0.001). In stage II colon cancer, there was a tendency toward improved DFS for dMMR patients (dMMR: 57.14 (95% CI 54.66-59.62) vs. pMMR 53.54 (95% CI 51.48-55.60), p=0.015, multivariate Cox regression HR 0.24 (95% CI 0.06-1.04), p=0.057). CD3, CD8, and PD-L1 expression was not associated with prognosis of dMMR patients. Multivariate Cox regression analysis showed a significant interaction between the MMR phenotype and stage (p=0.001).
CONCLUSION
dMMR is associated with an improved prognosis in stage II colon cancer but is no longer associated with a favorable prognosis in stage III colon cancer.
引言
错配修复缺陷（dMMR）或高度微卫星不稳定（MSI-H）与II期结肠癌预后改善相关，但与IV期结肠癌预后不良相关。dMMR在III期结肠癌中的临床意义尚未明确。
方法
对544例具有临床病理和生存数据的II期和III期结肠癌患者的组织微阵列（TMA）进行错配修复（MMR）蛋白、CD3、CD8和程序性死亡配体-1（PD-L1）染色。回顾患者的预后情况。
结果
在III期结肠癌中，dMMR是无病生存期（DFS）较差的标志物（Kaplan-Meier法，平均生存月数：dMMR为28.76（95%CI 18.46 - 39.05），pMMR为40.91（37.20 - 44.63），p = 0.014，多因素Cox回归：风险比（HR）4.17（95%CI 2.02 - 8.61），p < 0.001）。在II期结肠癌中，dMMR患者的DFS有改善趋势（dMMR为57.14（95%CI 54.66 - 59.62），pMMR为53.54（95%CI 51.48 - 55.60），p = 0.015，多因素Cox回归HR 0.24（95%CI 0.06 - 1.04），p = 0.057）。CD3、CD8和PD-L1表达与dMMR患者的预后无关。多因素Cox回归分析显示MMR表型与分期之间存在显著交互作用（p = 0.001）。
结论
dMMR与II期结肠癌预后改善相关，但与III期结肠癌的良好预后不再相关。
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