Screening of MSI detection loci and their heterogeneity in East Asian colorectal cancer patients
Screening of MSI detection loci and their heterogeneity in East Asian colorectal cancer patients
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DOI：
10.1002/cam4.2111
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发表时间：
2019-05-01
期刊：
影响因子：
4
通讯作者：
Xi, Yanfeng
中科院分区：
文献类型：
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作者：
Bai, Wenqi;Ma, Jinfeng;Xi, Yanfeng
目的本研究旨在筛选适合东亚结直肠癌患者的MSI检测位点。并探讨其瘤内异质性。方法收集结直肠癌病理组织标本271例。使用具有不同检测位点的不同PCR试剂盒检测MSI状态。然后，将结果与免疫组织化学（IHC）染色结果进行比较。对检测到MSI-H的病理组织标本进行显微解剖，以检查MSI状态是否存在瘤内异质性。结果271例中39例为dMMR。 dMMR 主要发生在右半结肠癌患者中（P < 0.0001）。与dMMR患者相比，pMMR患者临床分期更倾向于晚期并有淋巴结转移（P < 0.0001）。 MSI-H 肿瘤与 KRAS 突变（P = 0.036）和 PD-L1 表达（P = 0.038）显着相关。与Promega panel和24位点检测相比，NCI MSI panel和IHC染色结果一致性最高，Kappa值为0.850。随着检测位点的增加，检测灵敏度从87.18%下降到56.41%。单位点分析显示，敏感性最高的前两个位点均为单核苷酸位点，即BAT-26（95.45%）和BAT-25（86.36%）。灵敏度最高的二核苷酸位点是 D2S123 (50%)。 MSI-H的主要检测位点未表现出瘤内异质性。结论 2个单核苷酸位点（BAT25、BAT26）和3个二核苷酸位点（D2S123、D5S346、D17S250）的组合可能是最适合东亚人群MSI检测的位点。主要 MSI 位点不存在瘤内异质性。
Objective This study aims to screen the MSI detection loci suitable for the East Asian colorectal cancer patients. and explore its intratumoral heterogeneity. Methods A total of 271 pathological tissues specimens of colorectal cancer were collected. The MSI status was detected using different PCR reagent kits with different detection loci. Then, the results were compared with the immunohistochemical (IHC) staining results. Microdissection of pathological tissues specimens detected to be MSI-H was performed to examine whether there was intratumoral heterogeneity of MSI status. Results Thirty-nine out of 271 cases were dMMR. dMMR occurred mostly in patients with right-hemi colon cancer (P < 0.0001). Compared with dMMR patients, the clinical stages of pMMR patients were more inclined to be in the late stage with lymph node metastasis (P < 0.0001). MSI-H tumors were significantly associated with KRAS mutation (P = 0.036) and PD-L1 expression (P = 0.038). Compared with Promega panel and 24-locus detection, the consistency between NCI MSI panel and IHC staining results were the highest with the Kappa value of 0.850. The sensitivity of detection decreased from 87.18% to 56.41% with the increase in detection loci. Single locus analysis showed that the first two loci with the highest sensitivity were both mononucleotide loci, namely, BAT-26 (95.45%) and BAT-25 (86.36%). The dinucleotide locus with highest sensitivity was D2S123 (50%). The main detection loci of MSI-H showed no intratumoral heterogeneity. Conclusion The combination of 2 mononucleotide loci (BAT25, BAT26) and 3 dinucleotide loci (D2S123, D5S346, D17S250) might be the most suitable loci for MSI detection in East Asian population. There is no intratumoral heterogeneity in the main MSI loci.