PMS2基因胚系突变结直肠癌患者免疫组化及微卫星不稳定的表达

目的 分析PMS2基因胚系突变结直肠癌患者的免疫组化及微卫星不稳定表达特征.方法 对符合Amsterdam Ⅱ、修订Bethesda标准、微卫星高度不稳定、免疫组化MMR蛋白表达阴性的结直肠癌患者使用二代测序进行MMR基因胚系突变检测.结果 共检测出PMS2胚系突变27例,其中致病性突变4例,意义未明突变23例.4例致病性突变均表现为PMS2免疫组化单独表达缺失及高度微卫星不稳定.意义未明突变患者中33.3%(7/21)表现为PMS2表达缺失,52.6%(10/19)表现为高度微卫星不稳定.结论 PMS2基因致病性胚系突变结直肠癌倾向于表现为相应蛋白单独表达阴性.PMS2基因意义未明突变相应的表型多变,致病性分类尚需更进一步资料.

Immunohistochemistry and microsatellite instability profile of colorectal cancer with PMS2 germline mutation in Chinese population

Objective To investigate the characteristic of immunohistochemistry and microsatellite instability in colorectal cancer patients with PMS2 germline mutation.Methods Colorectal cancer patients, who met any of the following criteria, including Amsterdam Criteria Ⅱ or revised Bethesda Guidelines, MSI-H or loss expression of any MMR proteins, were enrolled for mismatch repair gene germline mutation test using targeted next-generation sequencing.Results Twenty-seven PMS2 germline mutation cases were found, including 4 pathogenic mutations and 23 variants of uncertain significance.Isolated loss of PMS2 expression and MSI-H were observed in all 4 pathogenic mutation cases.Seven of 21 tested VUS cases demonstrated loss of PMS2 expression.MSI-H was observed in 10 of 19 VUS probands.Only 5 of 21 VUS cases presented with concordant loss of PMS2 expression and MSI-H.Conclusion Pathogenic germline PMS2 mutation is likely to exhibit solitary deficient expression of PMS2.Phenotype of PMS2 VUS varies, which should be interpreted with cautiousness.