Berardinelli Gustavo Noriz, Scapulatempo-Neto Cristovam, Durães Ronílson, Antônio de Oliveira Marco, Guimarães Denise, Reis Rui Manuel
Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
Department of Oncology, Barretos Cancer Hospital, Jales, São Paulo, Brazil.
Oncotarget. 2018 Jun 19;9(47):28691-28701. doi: 10.18632/oncotarget.25611.
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, (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. (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 (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 (T17) corroborate the molecular findings. This study suggests the use of molecular assays over IHC for MSI analysis and proposes the inclusion (T17) marker as a complementary analysis in discordant cases.
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CRC的一种遗传途径，与特定的临床病理特征相关，并且最近成为免疫治疗反应的主要生物标志物。关于巴西CRC患者中MSI的频率，几乎没有相关信息，而且在资源有限的国家中，MSI筛查的理想方法仍存在争议。我们建议通过分子和免疫组织化学（IHC）方法评估MSI，比较这两种方法，并评估一种新型微卫星标记物（T17）的适用性。对总共1013例CRC患者使用PCR多重检测板进行分子MSI评估。通过IHC评估错配修复（MMR）蛋白（MLH1、MSH2、MSH6和PMS2）的表达。通过片段分析对（T17）标记物进行分析。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功能正常，10.2%为MMR缺陷，0.9%为不确定。对106例MSI阳性和215例MSI阴性病例进行的（T17）基因分型显示，其改变仅在MSI阳性病例中出现。我们观察到分子和IHC两种方法之间具有一致性（0.956，kappa检验），仅有8个不一致的结果，并且在这部分病例中，（T17）证实了分子检测结果。本研究表明，在MSI分析中，分子检测方法优于IHC，并建议将（T17）标记物作为不一致病例的补充分析方法。
