MLH1甲基化与胰腺实性假乳头肿瘤远处转移的相关性研究

Correlation between MLH1 methylation and distant metastasis of solid pseudopapillary tumor of pancreas

目的观察转移性胰腺实性假乳头肿瘤(SPT)和非转移性SPT组织中MLH1蛋白表达及MLH1基因甲基化的临床意义, 探讨MLH1基因甲基化与SPT发生转移的相关性。方法回顾性研究2009年1月至2022年5月北京大学人民医院、日照市中心医院、辽宁省朝阳市中心医院收治的转移性SPT患者12例作为研究组, 其中男性3例、女性9例, 中位年龄47岁, 年龄范围21~73岁。筛选2009年1月至2017年5月北京大学人民医院病理库中诊断明确、病史清晰、随访资料完整的非转移性SPT患者30例作为对照组, 其中男性12例、女性18例, 中位年龄42岁, 年龄范围34~69岁。收集患者性别、年龄、病理资料等临床资料。取病理组织蜡块分别检测MLH1蛋白的免疫组织化学表达和MLH1基因的甲基化。结果两组SPT患者一般资料比较, 差异无统计学意义(均P>0.05)。12例转移性SPT患者中, 转移至肝脏4例, 脾脏2例, 肺2例, 淋巴结内2例, 纵隔1例, 骶骨1例。与非转移性SPT组织中MLH1蛋白缺失率0(0/30)比较, 转移性胰腺病灶(转移性SPT-P)和转移灶(转移性SPT-M)中MLH1蛋白缺失率[均为33.3%(4/12)]均增加, 差异具有统计学意义(均χ^(2)=5.00, 均P=0.041)。与非转移性SPT组织中MLH1基因甲基化阳性率0(0/30)比较, 转移性SPT-M和转移性SPT-P中MLH1基因甲基化阳性率[均为30%(3/10)]均增高, 差异有统计学意义(均χ^(2)=0.96, 均P=0.032)。结论与非转移性SPT相比, MLH1蛋白表达缺失率和MLH1基因甲基化在转移性SPT组织中升高。MLH1基因甲基化可能发生在SPT转移前, 可作为SPT的转移预测指标。

Objective To investigate the significance of MLH1 protein expression and MLH1 gene methylation rate between metastatic solid pseudopapillary tumor of pancreas(SPT)and non-metastatic SPT,and to explore the correlation between MLH1 gene methylation and SPT metastasis.Methods Twelve metastatic SPT patients admitted to Peking University People's Hospital,Rizhao Central Hospital and Chaoyang Central Hospital of Liaoning Province from January 2009 to May 2022 were studied retrospectively,including 3 males and 9 females,with a median age of 47 years old,ranging from 21 to 73 years old.Thirty non-metastatic SPT patients with clear diagnosis,clear medical history and complete follow-up data from pathological database of Peking University People's Hospital from January 2009 to May 2017 were selected as the control group,including 12 males and 18 females,with a median age of 42 years old,ranging from 34 to 69 years old.Clinical data such as gender,age and pathological data were collected.Immunohistochemical expression of MLH1 protein and methylation of MLH1 gene were detected by pathological paraffins.Results There was no significant difference in general data between the two groups(all P>0.05).Among the 12 metastatic SPT patients,4 cases metastasized to liver,2 to spleen,2 to lung,2 to lymph nodes,1 to mediastinum,and 1 to sacrum.Compared with the non-metastatic tissue,the MLH1 protein deletion in metastatic pancreatic lesions(metastatic SPT-P)and metastatic lesions(metastatic SPT-M)were increased[both 33.3%(4/12)],and the difference was statistically significant(both Chi square=5.00,both P=0.041).Compared with 0(0/30)MLH1 gene methylation rate in non-metastatic SPT tissues,the methylation rate of MLH1 gene in metastatic SPT-M and metastatic SPT-P tissues[both 30%(3/10)]were higher,with statistical significance(both Chi square=0.96,both P=0.032).Conclusion Compared with non-metastatic SPT,the loss rate of MLH1 protein expression and MLH1 gene methylation are increased in metastatic SPT.MLH1 methylation may occur before metastasis,which can be used as a predictor of SPT metastasis.