Alqahtani Masood, Grieu Fabienne, Carrello Amerigo, Amanuel Benhur, Mashour Miral, Alattas Rabab, Alsaleh Khalid, Alsheikh Abdulmalik, Alqahtani Sarah, Iacopetta Barry
School of Surgery, University of Western Australia, Perth, Australia E-mail : barry.
Asian Pac J Cancer Prev. 2016;17(4):1917-23. doi: 10.7314/apjcp.2016.17.4.1917.
Lynch Syndrome (LS) is a familial cancer condition caused by germline mutations in DNA mismatch repair genes. Individuals with LS have a greatly increased risk of developing colorectal cancer (CRC) and it is therefore important to identify mutation carriers so they can undergo regular surveillance. Tumor DNA from LS patients characteristically shows microsatellite instability (MSI). Our aim here was to screen young CRC patients for MSI as a first step in the identification of unrecognized cases of LS in the Saudi population.
Archival tumor tissue was obtained from 284 CRC patients treated at 4 institutes in Dammam and Riyadh between 2006 and 2015 and aged less than 60 years at diagnosis. MSI screening was performed using the BAT-26 microsatellite marker and positive cases confirmed using the pentaplex MSI analysis system. Positive cases were screened for BRAF mutations to exclude sporadic CRC and were evaluated for loss of expression of 4 DNA mismatch repair proteins using immunohistochemistry.
MSI was found in 33/284 (11.6%) cases, of which only one showed a BRAF mutation. Saudi MSI cases showed similar instability in the BAT-26 and BAT-25 markers to Australian MSI cases, but significantly lower frequencies of instability in 3 other microsatellite markers.
MSI screening of young Saudi CRC patients reveals that approximately 1 in 9 are candidates for LS. Patients with MSI are strongly recommended to undergo genetic counselling and germline mutation testing for LS. Other affected family members can then be identified and offered regular surveillance for early detection of LS-associated cancers.
林奇综合征（LS）是一种由DNA错配修复基因种系突变引起的家族性癌症疾病。患有LS的个体患结直肠癌（CRC）的风险大大增加，因此识别突变携带者很重要，以便他们能够接受定期监测。LS患者的肿瘤DNA特征性地显示微卫星不稳定性（MSI）。我们的目的是筛查年轻的CRC患者是否存在MSI，作为在沙特人群中识别未被认识的LS病例的第一步。
从2006年至2015年在达曼和利雅得的4家机构接受治疗且诊断时年龄小于60岁的284例CRC患者中获取存档肿瘤组织。使用BAT-26微卫星标记进行MSI筛查，阳性病例使用五重MSI分析系统进行确认。对阳性病例进行BRAF突变筛查以排除散发性CRC，并使用免疫组织化学评估4种DNA错配修复蛋白的表达缺失。
在33/284（11.6%）例中发现MSI，其中只有1例显示BRAF突变。沙特MSI病例在BAT-26和BAT-25标记中的不稳定性与澳大利亚MSI病例相似，但在其他3个微卫星标记中的不稳定性频率显著较低。
对年轻沙特CRC患者进行MSI筛查显示，约九分之一的患者可能患有LS。强烈建议MSI患者接受遗传咨询和LS的种系突变检测。然后可以识别其他受影响的家庭成员，并为其提供定期监测，以便早期发现与LS相关的癌症。
