肺神经内分泌肿瘤中INSM1的表达及其临床意义

Expression of INSM1 in pulmonary neuroendocrine tumors and its clinicopathologic significance

目的探讨胰岛素瘤相关蛋白1(insulinoma-associated protein 1,INSM1)在肺神经内分泌肿瘤中的表达及其在鉴别诊断中的意义。方法采用免疫组化EnVision两步法检测INSM1、Syn、CgA、CD56在肺小细胞癌(26例)、肺大细胞神经内分泌癌(23例)、肺类癌(23例)、肺腺癌(72例)及肺鳞癌(52例)中的表达。结果(1)INSM1在神经内分泌肿瘤中的总阳性率为87.5%,显著高于肺腺癌(2.8%)和肺鳞癌(1.9%)(P<0.0001)。(2)INSM1在肺小细胞癌和大细胞神经内分泌癌中的敏感性分别为88.5%和78.3%,与Syn(88.5%和82.6%)及CD56(88.5%和78.3%)相似,显著高于CgA(57.7%和39.1%)(P<0.0001);INSM1在肺类癌中的敏感性为95.6%,与传统的神经内分泌免疫组化标志物(Syn、CgA、CD56)相似(P>0.999)。(3)INSM1在肺腺癌和肺鳞癌中的阳性率分别为2.8%和1.9%,与Syn和CgA相比差异无显著性(P>0.05),显著高于CD56(P<0.05)。(4)在37℃1 h孵育一抗,INSM1在小细胞癌、大细胞神经内分泌癌和肺类癌中的阳性率分别为84.6%、52.2%和30%;在4℃孵育一抗过夜,INSM1在三者中的阳性率分别为88.5%、78.3%和95.6%;一抗在4℃孵育过夜条件下,INSM1阳性率均高于37℃1 h的孵育条件。在4℃过夜和37℃1 h两种不同孵育条件下,小细胞癌的检测结果一致性为0.8354,大细胞神经内分泌癌为0.2868,肺类癌为0.0390。结论INSM1是肺神经内分泌肿瘤比较可靠的标志物,在4℃过夜条件下孵育一抗的检测结果比较可信。

Purpose To investigate the insulinoma-associated protein 1(INSM1)expression in pulmonary neuroendocrine tumors and its role on differential diagnosis.Methods Expression of INSM1,Syn,CgA,CD56 was tested using immunohistochemical EnVision two-step method in 26 cases of small cell lung carcinoma,23 cases of large cell neuroendocrine carcinoma,23 cases of carcinoid tumors,72 cases of lung adenocarcinoma,and 52 cases of lung squamous carcinoma.Result(1)The expression of INSM1 in lung neuroendocrine neoplasms(87.5%)was higher than that of lung adenocarcinoma(2.8%)and lung squamous carcinoma(1.9%)(P<0.0001).(2)For small cell lung carcinoma and large cell neuroendocrine carcinoma,the sensitivity of INSM1(88.5%and 78.3%)was similar to Syn(88.5%and 82.6%)and CD56(88.5%and 78.3%)but considerably higher than CgA(57.7%and 39.1%)(P<0.0001).The sensitivity of INSM1 in carcinoid tumors was 95.6%,similar to the conventional markers(Syn,CgA and CD56)(P>0.999).(3)INSM1 stained 2.8%of lung adenocarcinoma and 1.9%of lung squamous carcinoma,which was comparable to Syn and CgA but higher than CD56(P<0.05).(4)After incubation at 37℃for 1 h,the positive rate of INSM1 in small cell lung carcinoma,large cell neuroendocrine carcinoma and carcinoid tumors were 84.6%,52.2%and 30%,respectively.When primary antibody was incubated overnight at 4℃,the positive rates of INSM1 in the three groups were 88.5%,78.3%and 95.6%,respectively.The positive rate of INSM1 incubated overnight at 4℃was higher than that at 37℃for 1 h.Under the conditions of overnight at 4℃and at 37℃for 1h,the consistency of INSM1 for small cell carcinoma,large cell neuroendocrine carcinoma and carcinoid tumor was 0.8354,0.2868 and 0.0390,respectively.Conclusion INSM1 is a reliable marker of lung neuroendocrine neoplasms,and the detection of INSM1 incubated overnight at 4℃is more reliable.