Clark A J, Barnetson R, Farrington S M, Dunlop M G
Colon Cancer Genetics Group, Academic Coloproctology, Division of Oncology, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Fam Cancer. 2004;3(2):85-91. doi: 10.1023/B:FAME.0000039915.94550.cc.
Microsatellite instability (MSI) in colorectal tumours is the hallmark of defective DNA mismatch repair (MMR) and high level MSI can be detected in up to 15% of incident colorectal cancers. MSI in sporadic colorectal tumours is primarily due to epigenetic silencing of MLH1 while MSI is almost universal in tumours from HNPCC family members due to germline MMR gene mutation with loss or mutational inactivation of the second copy as a somatic event. There is evidence that tumour MSI is associated with a better outcome than the generality of large bowel malignancy. However, although MSI occurs in both sporadic colorectal cancer and in tumours arising in patients with germline MMR gene mutations, cancer survival should not be considered to be equivalent for these two groups with MSI tumours simply because both exhibit similarities in molecular phenotype. Here, we review the evidence on prognosis in patients with sporadic MSI tumours compared to those who have inherited a germline DNA MMR repair gene defect. In addition, we explore whether there are variables that afford opportunity to distinguish three groups on the basis of MSI status, namely: sporadic MSI tumours; MSI tumours in carriers of germline MMR gene defects; microsatellite stable (MSS) tumours. Differences in prognosis between these three groups is important because it underpins the rationale for surveillance and early identification of tumours in MMR gene carriers, as well as refining understanding of the influence of MSI on cancer progression. Furthermore, we discuss the effect of MSI on the effectiveness of chemotherapy regimens.
结直肠癌中的微卫星不稳定性（MSI）是DNA错配修复（MMR）缺陷的标志，高达15%的初发性结直肠癌可检测到高水平的MSI。散发性结直肠癌中的MSI主要是由于MLH1的表观遗传沉默，而由于种系MMR基因突变，HNPCC家族成员的肿瘤中MSI几乎普遍存在，第二个拷贝作为体细胞事件发生缺失或突变失活。有证据表明，与大多数大肠恶性肿瘤相比，肿瘤MSI与更好的预后相关。然而，尽管MSI既发生在散发性结直肠癌中，也发生在种系MMR基因突变患者的肿瘤中，但这两组MSI肿瘤患者的癌症生存率不应被认为是等同的，仅仅因为它们在分子表型上表现出相似性。在这里，我们回顾了散发性MSI肿瘤患者与那些遗传了种系DNA MMR修复基因缺陷患者的预后证据。此外，我们探讨是否存在一些变量，有机会根据MSI状态区分三组，即：散发性MSI肿瘤；种系MMR基因缺陷携带者中的MSI肿瘤；微卫星稳定（MSS）肿瘤。这三组之间的预后差异很重要，因为它为MMR基因携带者中肿瘤的监测和早期识别提供了理论依据，同时也有助于深化对MSI对癌症进展影响的理解。此外，我们还讨论了MSI对化疗方案疗效的影响。
