医脉通编译整理，转载请务必注明出处。
微卫星不稳定性（microsatellite instability，MSI）是指与正常组织相比，在肿瘤中某一微卫星由于重复单位的插入或缺失而造成的微卫星长度的任何改变，出现新的微卫星等位基因现象。近期，Erin Schenk教授（血液/肿瘤医生，毕业于梅奥研究生学院）在接受采访时，对微卫星不稳定性在实体瘤中的作用进行讨论，医脉通整理如下：
人类基因组准确性是通过DNA修复多种途径维持，这些途径对DNA损伤或复制错误会产生应答。错配修复（MMR）蛋白可以校正新复制的DNA链，避免碱基配对错误和在DNA复制过程中由于模板链滑动发生的核苷酸小缺失或插入。复制错误被发现时，MMR蛋白会删除不正确核苷酸，同时修复因核苷酸缺失产生的空位。据估计，MMR蛋白会提高DNA复制准确度好几个数量级。
一种主要的MMR蛋白突变可能导致DNA错误积累，使后续DNA复制周期复杂。基因组内重复元件对MMR蛋白功能障碍特别敏感，这些重复元件的核苷酸重复序列增加或损失被称为微卫星不稳定性（MSI）。
随着点突变和MSI负担增加，基因组稳定性丧失，细胞积累恶性性质。这种细胞失调的结果在Lynch综合征（携带一种MMR蛋白的种系突变）患者中可以清楚地观察到。这些患者最常见的是进展为结直肠癌，携带这些突变的女性也处于子宫内膜癌和卵巢癌的重大风险中。Lynch综合征患者的胃癌、胰腺癌、小肠癌、尿路上皮癌和脑胶质瘤风险增加。
MMR蛋白体细胞突变以及引起的MSI-H（卫星不稳定性-高）状态会对结直肠癌患者有明显影响。MSI-H状态在II期结肠癌中最为常见，被认为是良好预后的标志。与微卫星不稳定低或缺失的结肠癌相比较，II期MSI-II结肠癌接受单纯手术的复发可能性降低。
总体而言，数据表明辅助化疗在MSI-H的II期结肠癌中不会改善已经获得的良好结局。这些患者的良好结局被认为是由于产生抗肿瘤反应的结果，表现为肿瘤浸润性淋巴细胞的较高水平。偶尔情况下，MSI-H结肠癌会逃避内源性免疫反应，发展为转移性病变。即使在转移性情况下，局部肿瘤免疫浸润会发挥疾病控制潜力。
局部肿瘤微环境分析证明MSI-H结肠癌包含大量表达抑制分子的免疫细胞，包括PD-L1。以早期临床试验数据为基础的结果显示，在转移性MSI-H结肠癌患者中，包含检查点抑制剂的治疗会带来显著的总缓解率。
在非结直肠癌中，MSI-H状态对治疗决策的影响是有限的。令人鼓舞的是，在一项II期临床试验中，伴有一种MMR蛋白突变的转移性胆管癌、小肠癌或子宫内膜癌患者会表现出对pembrolizumab的反应。对于早期病变的MSI-H非结直肠癌来说，无论MSI状态是否会影响化疗的需求，还需要额外的前瞻性数据。
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