微卫星不稳定性和错配修复蛋白缺乏症:同样的预测标志物?

Maja L. Nádorvári, Gábor Lotz, Janina Kulka, András Kiss, József Tímár
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摘要

目前的临床指南推荐将错配修复(MMR)蛋白免疫组化(IHC)或分子微卫星不稳定性(MSI)检测作为免疫疗法的预测指标。大多数病理指南认为,MMR 蛋白免疫组化(IHC)是鉴别 MMR 缺乏癌症的金标准检测方法,并建议仅在特殊情况下或筛查林奇综合征时进行分子 MSI 检测。然而,有文献数据表明,这两种检测方法可能并不等同。例如,分子流行病学研究报告称,在不同类型的癌症中,缺乏 MMR(dMMR)和 MSI 的比例不同。此外,对这两种检测方法进行直接比较后发现,MMR IHC 和 MSI 检测之间经常出现差异,尤其是在非结肠直肠癌和非子宫内膜癌中,以及在具有不寻常 dMMR 表型的病例中。还有零星的临床数据显示,如果根据癌症的 dMMR 与 MSI 状态来选择患者,免疫检查点抑制剂的疗效就会不同。所有这些观察结果都对目前的教条提出了质疑,即 dMMR 表型和遗传 MSI 状态同样是免疫疗法的预测指标。
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Microsatellite instability and mismatch repair protein deficiency: equal predictive markers?
Current clinical guidelines recommend mismatch repair (MMR) protein immunohistochemistry (IHC) or molecular microsatellite instability (MSI) tests as predictive markers of immunotherapies. Most of the pathological guidelines consider MMR protein IHC as the gold standard test to identify cancers with MMR deficiency and recommend molecular MSI tests only in special circumstances or to screen for Lynch syndrome. However, there are data in the literature which suggest that the two test types may not be equal. For example, molecular epidemiology studies reported different rates of deficient MMR (dMMR) and MSI in various cancer types. Additionally, direct comparisons of the two tests revealed relatively frequent discrepancies between MMR IHC and MSI tests, especially in non-colorectal and non-endometrial cancers and in cases with unusual dMMR phenotypes. There are also scattered clinical data showing that the efficacy of immune checkpoint inhibitors is different if the patient selection was based on dMMR versus MSI status of the cancers. All these observations question the current dogma that dMMR phenotype and genetic MSI status are equal predictive markers of the immunotherapies.
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