Advantage of HSP110 (T17) marker inclusion for microsatellite instability (MSI) detection in colorectal cancer patients.
Advantage of HSP110 (T17) marker inclusion for microsatellite instability (MSI) detection in colorectal cancer patients.
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DOI：
10.18632/oncotarget.25611
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发表时间：
2018-06-19
期刊：
影响因子：
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通讯作者：
Reis, Rui Manuel
中科院分区：
文献类型：
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作者：
Berardinelli, Gustavo Noriz;Scapulatempo-Neto, Cristovam;Reis, Rui Manuel
结直肠癌（CRC）是全球癌症死亡的主要原因。微卫星不稳定性（MSI）是导致结直肠癌的遗传途径，与特定的临床病理特征相关，最近成为免疫治疗反应的主要生物标志物。巴西CRC患者中MSI频率的信息很少，在资源有限的国家进行MSI筛查的理想方法仍然存在争议。我们建议通过分子和免疫组织化学（IHC）方法来评估MSI，比较两种方法，并评估一种新的微卫星标记HSP 110（T17）的纳入。采用多重PCR方法对1013例CRC患者进行MSI分子水平的检测。通过IHC评估错配修复（MMR）蛋白（MLH1、MSH2、MSH6和PMS2）表达。HSP110（T17）标记物采用片段分析法。在分子水平上，89.5%的病例为MSI阴性，10.5%为MSI阳性。IHC显示88.9%的病例表现为MMR熟练状态，10.2%为MMR缺陷，0.9%为不确定状态。对106例MSI阳性和215例MSI阴性患者的HSP110（T17）基因分型结果显示，T17基因仅在MSI阳性患者中有改变。我们观察到分子和IHC方法之间的一致性（0.956，Kappa检验），只有8个不一致的结果，并且在这个病例子集中，HSP 110（T17）证实了分子结果。这项研究建议使用分子检测在IHC MSI分析，并提出了包括HSP 110（T17）标志物作为一种补充分析不一致的情况下。
Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Microsatellite instability (MSI) is a genetic pathway leading to CRC, associated with particular clinicopathological features, and recently a major biomarker of immunotherapy response. There is little information the frequency MSI among Brazilian CRC patients, and it is still debatable the ideal methodology for MSI screening in countries with limited resources. We proposed to evaluate MSI by molecular and immunohistochemistry (IHC) methods, to compare both methodologies and also to assess the inclusion of a novel microsatellite marker, HSP110 (T17). The molecular MSI evaluation was performed using a PCR-multiplex panel in a total of 1013 CRC patients. Mismatch repair (MMR) proteins (MLH1, MSH2, MSH6 and PMS2) expression were evaluated by IHC. HSP110 (T17) marker was analyzed by fragment analysis. Molecularly, 89.5% of cases were MSI-negative and 10.5% were MSI-positive. The IHC showed that 88.9% of cases exhibited MMR-proficient status, 10.2% were MMR-deficient and 0.9% was inconclusive. Genotyping of the HSP110 (T17) in 106 MSI-positive and 215 MSI-negative cases showed its alteration only among the MSI-positive cases. We observed agreement (0.956, Kappa Test) between both molecular and IHC methodologies, with only eight discordant results, and in this subset of cases the HSP110 (T17) corroborate the molecular findings. This study suggests the use of molecular assays over IHC for MSI analysis and proposes the inclusion HSP110 (T17) marker as a complementary analysis in discordant cases.