CD200和INSM1在胃肠胰神经内分泌肿瘤中的表达及其病理诊断价值

Expression of CD200 and INSM1 in gastrointestinal and pancreatic neuroendocrine neoplasms and its diagnostic values

目的探讨CD200和胰岛素瘤相关蛋白1(INSM1)在胃肠胰神经内分泌肿瘤(NEN)中的表达及病理诊断价值。方法采用免疫组织化学方法在69例胃肠胰NEN,66例胃肠胰非NEN和16例转移性NEN中检测CD200、INSM1、突触素和嗜铬粒素A(CgA)的表达情况,并通过绘制受试者工作特征(ROC)曲线,比较CD200、INSM1、突触素和CgA及其组合在胃肠胰NEN中的病理诊断价值。结果CD200的阳性信号位于肿瘤细胞胞质和/或胞膜,CD200在胃肠胰NEN和非NEN中的阳性表达率差异有统计学意义(P<0.01)。CD200对诊断胃肠胰NEN的灵敏度为95.7%,特异度为78.8%。CD200在神经内分泌瘤和神经内分泌癌中的阳性率差异有统计学意义(P=0.05)。INSM1阳性信号位于肿瘤细胞核,INSM1在胃肠胰NEN和非NEN中的阳性表达率差异有统计学意义(P<0.01)。INSM1对诊断胃肠胰NEN的灵敏度为85.5%,特异度为95.5%。INSM1在神经内分泌瘤和神经内分泌癌中的阳性率,在神经内分泌瘤G1和G3中的阳性率差异均有统计学意义(P<0.05)。单项检测CD200、INSM1、突触素和CgA ROC曲线下面积(0.857、0.907、0.890和0.833)差异无统计学意义(P>0.05)。联合检测CD200+INSM1的灵敏度明显高于突触素+CgA(85.5%比63.8%,P<0.05),两种组合的ROC曲线下面积分别为0.962和0.925,两者间的差异无统计学意义(P>0.05)。结论CD200和INSM1是两种新型NEN标志物,有助于胃肠胰NEN的诊断和排除其相似的肿瘤,并且可以提示肿瘤的分化级别。联合检测CD200和INSM1作为免疫组织化学小组时具有高灵敏度和特异度,可以作为突触素和CgA有用的补充。

Objective To investigate the expression and diagnostic values of CD200 and insulinoma associated protein 1(INSM1)in gastrointestinal and pancreatic neuroendocrine neoplasm(GIP-NEN).Methods The expression of CD200,INSM1,Syn and CgA was detected in 69 cases of GIP-NEN,66 cases of gastrointestinal and pancreatic non-neuroendocrine neoplasm(GIP-nonNEN)and 16 cases of metastatic neuroendocrine neoplasm by immunohistochemistry,to compare the values of CD200,INSM1,Syn,CgA and their combinations in diagnosing GIP-NEN.Receiver operating characteristics(ROC)curve was used.Results The immunoreactivity of CD200 was present in the cytoplasma and/or membrane of the neoplasms cells,the positive expression rates in GIP-NEN and GIP-nonNEN were significantly different(P<0.01).The sensitivity and specificity of CD200 for diagnosing GIP-NEN were 95.7%and 78.8%,respectively.There was significant difference of the positive rates of CD200 between neuroendocrine tumor and neuroendocrine carcinoma(P=0.05).The immunoreactivity of INSM1 was present in the nuclei of neoplasms cells.The positive expression rates in GIP-NEN and GIP-nonNEN were significantly different(P<0.01).The sensitivity and specificity of INSM1 for diagnosis of GIP-NEN were 85.5%and 95.5%,respectively.There were also significantly different positive rates of INSM1 between neuroendocrine tumor and neuroendocrine carcinoma,as well as between G1 and G3 neuroendocrine tumors(P<0.05).There was no difference in the area under ROC curve(AUC)of single stain of CD200,INSM1,Syn or CgA(0.857,0.907,0.890 and 0.833,respectively,P>0.05).The sensitivity of combined CD200+INSM1 stains for diagnosing GIP-NEN was significantly higher than that of Syn+CgA(85.5%vs.63.8%,P<0.05).The AUC of two combinations were 0.962 and 0.925,respectively,which were not statistically different(P>0.05).Conclusions CD200 and INSM1 are two novel markers of neuroendocrine neoplasm,which aid to diagnosis for GIP-NEN and exclude its mimickers.They are associated with tumor grades.Combining both as an immunohistochemical panel shows high sensitivity and specificity.Thus,the combined panel can be utilized as useful supplement for Syn and CgA.