INSM1在胃肠胰神经内分泌肿瘤诊断中的价值
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摘要
目的探讨胰岛素瘤相关蛋白1(insulinoma-associated protein 1,INSM1)在胃肠胰神经内分泌肿瘤(gastroenteropancreatic neuroendocrine neoplasms,GEP-NEN)中的表达及其在诊断中的应用价值。方法应用免疫组化En Vision法检测48例GEPNEN和40例胃肠胰非神经内分泌肿瘤中INSM1、Cg A、Syn和CD56的表达,并分析其与GEP-NEN临床病理特征的关系。结果48例GEP-NEN中,INSM1的阳性率为81. 3%,而Cg A、Syn和CD56的阳性率分别为50%(24/48)、89. 9%(43/48)和66. 7%(32/48),INSM1、Cg A、Syn和CD56在胃肠胰非神经内分泌瘤中的阳性率分别为0 (0/40)、10. 0%(4/40)、12. 5%(5/40)和10%(4/40),INSM1、Cg A、Syn和CD56在GEP-NEN中的表达均明显高于胃肠胰非神经内分泌瘤中的表达(P <0. 05);INSM1主要表达于食管、胰腺和结直肠神经内分泌肿瘤中,与Cg A、Syn和CD56表达不同,INSM1表达与GEP-NEN分级无关(P> 0. 05)。INSM1对GEP-NEN诊断的灵敏度高于Cg A,特异度与Cg A、Syn和CD56差异无统计学意义(P> 0. 05)。结论INSM1属于新的神经内分泌标志物,可与Cg A、Syn和CD56联合检测用于GEP-NEN的诊断。
Purpose To investigate the expression of insulinoma-associated protein 1( INSM1) in gastroenteropancreatic neuroendocrine neoplasms( GEP-NEN) and its value of INSM1 in the diagnosis of GEP-NEN. Methods The expression of IN-SM1,Cg A,Syn and CD56 in 48 cases of GEP-NEN and 40 cases of non GEP-NEN was detected by En Vision immunohistochemical staining,and the correlation between INSM1 expression and clinicopathologic features was also analyzed. Results Of48 cases of GEP-NEN,the positive rate of INSM1 was 81. 3%,while the positive rates of Cg A,Syn and CD56 were 50%( 24/48),89. 9%( 43/48) and 66. 7%( 32/48),respectively. The positive rates of INSM1,Cg A,Syn and CD56 in GEP-NEN were0( 0/40),10%( 4/40),12. 5%( 5/40) and 10%( 4/40),respectively. The expression of INSM1,Cg A,Syn and CD56 in GEP-NEN was significantly higher than that in non GEP-NEN( P< 0. 05). Compared with Cg A,Syn and CD56,INSM1 was mainly expressed in esophageal,pancreatic and colorectal neuroendocrine tumors. INSM1 expression was unrelated to the grad-ing of GEP-NEN( P > 0. 05). The sensitivity of INSM1 in the diagnosis of GEP-NEN was higher than that of Cg A,but the specificity of was not significantly different from that of Cg A,Syn and CD56( P > 0. 05). Conclusion INSM1 is a new neuroendocrine marker that can be used in the diagnosis of gastrointestinal and pancreatic neuroendocrine tumors by combined detection of Cg A,Syn and CD56.
Purpose To investigate the expression of insulinoma-associated protein 1( INSM1) in gastroenteropancreatic neuroendocrine neoplasms( GEP-NEN) and its value of INSM1 in the diagnosis of GEP-NEN. Methods The expression of IN-SM1,Cg A,Syn and CD56 in 48 cases of GEP-NEN and 40 cases of non GEP-NEN was detected by En Vision immunohistochemical staining,and the correlation between INSM1 expression and clinicopathologic features was also analyzed. Results Of48 cases of GEP-NEN,the positive rate of INSM1 was 81. 3%,while the positive rates of Cg A,Syn and CD56 were 50%( 24/48),89. 9%( 43/48) and 66. 7%( 32/48),respectively. The positive rates of INSM1,Cg A,Syn and CD56 in GEP-NEN were0( 0/40),10%( 4/40),12. 5%( 5/40) and 10%( 4/40),respectively. The expression of INSM1,Cg A,Syn and CD56 in GEP-NEN was significantly higher than that in non GEP-NEN( P< 0. 05). Compared with Cg A,Syn and CD56,INSM1 was mainly expressed in esophageal,pancreatic and colorectal neuroendocrine tumors. INSM1 expression was unrelated to the grad-ing of GEP-NEN( P > 0. 05). The sensitivity of INSM1 in the diagnosis of GEP-NEN was higher than that of Cg A,but the specificity of was not significantly different from that of Cg A,Syn and CD56( P > 0. 05). Conclusion INSM1 is a new neuroendocrine marker that can be used in the diagnosis of gastrointestinal and pancreatic neuroendocrine tumors by combined detection of Cg A,Syn and CD56.
引文
[1]尔丽绵,吴明利,李勇,等.低增殖活性胃肠神经内分泌肿瘤组织中IMP3的表达及意义[J].临床与实验病理学杂志,2017,33(8):910-912.
[2] Liu W D,Wang H W,Muguira M,et al. INSM1 functions as a transcriptional repressor of the neuroD/beta2 gene through the recruitment of Cyclin D1 and histone deacetylases[J]. Biochem J,2006,397(1):169-177.
[3] Zhang T,Liu W D,Saunee N A,et al. Zinc finger transcription factor INSM1 interrupts cyclin D1 and CDK4 binding and induces cell cycle arrest[J]. J Biol Chem,2009,284(9):5574-5581.
[4] Wang H W,Muguira M,Liu W D,et al. Identification of an INSM1-binding site in the insulin promoter:negative regulation of the insulin gene transcription[J]. J Endocrinol,2008,198(1):29-39.
[5] Osipovich A B,Long Q,Manduchi E,et al. Insm1 promotes endocrine cell differentiation by modulating the expression of a network of genes that includes Neurog3 and Ripply3[J]. Development,2014,141(15):2939-2949.
[6] Fujino K,Motooka Y,Hassan W A,et al. Insulinoma-associated protein 1 is a crucial regulator of neuroendocrine differentiation in lung cancer[J]. Am J Pathol,2015,185(12):3164-3177.
[7] Wang H,Chen Y,Fernandez-Del Castillo C,et al. Heterogeneity in signaling pathways of gastroenteropancreatic neuroendocrine tumors:a critical look at notch signaling pathway[J]. Mod Pathol,2013,26(1):139-147.
[8] Fujino K,Yasufuku K,Kudoh S,et al. INSM1 is the best marker for the diagnosis of neuroendocrine tumors:comparison with CGA,SYP and CD56[J]. Int J Clin Exp Pathol,2017,10(5):5393-5405.
[9] Rosenbaum J N,Guo Z,Baus R M,et al. INSM1:a novel immunohistochemical and molecular marker for neuroendocrine and neuroepithelial neoplasms[J]. Am J Clin Pathol,2015,144(4):579-591.
[10] Rooper L M,Sharma R,Li Q K,et al. INSM1 demonstrates superior performance ti the individual and combined use of synaptophysin,chromogranin and CD56 for diagnosing neuroendocrine tumors of the thoracic cavity[J]. Am J Surg Pathol,2017,41(11):1561-1569.
[11] Rooper L M,Bishop J A,Westra W H. INSM1 is a sensitive and specific marker of neuroendocrine differentiation in head and neck tumors[J]. Am J Surg Pathol,2018,42(5):665-671.
[12] Tanigawa M,Nakayama M,Taira T,et al. Insulinoma-associated protein(INSM1)is a useful marker for pancreatic neuroendocrine tumor[J]. Med Mol Morphol,2018,51(1):32-40.
[2] Liu W D,Wang H W,Muguira M,et al. INSM1 functions as a transcriptional repressor of the neuroD/beta2 gene through the recruitment of Cyclin D1 and histone deacetylases[J]. Biochem J,2006,397(1):169-177.
[3] Zhang T,Liu W D,Saunee N A,et al. Zinc finger transcription factor INSM1 interrupts cyclin D1 and CDK4 binding and induces cell cycle arrest[J]. J Biol Chem,2009,284(9):5574-5581.
[4] Wang H W,Muguira M,Liu W D,et al. Identification of an INSM1-binding site in the insulin promoter:negative regulation of the insulin gene transcription[J]. J Endocrinol,2008,198(1):29-39.
[5] Osipovich A B,Long Q,Manduchi E,et al. Insm1 promotes endocrine cell differentiation by modulating the expression of a network of genes that includes Neurog3 and Ripply3[J]. Development,2014,141(15):2939-2949.
[6] Fujino K,Motooka Y,Hassan W A,et al. Insulinoma-associated protein 1 is a crucial regulator of neuroendocrine differentiation in lung cancer[J]. Am J Pathol,2015,185(12):3164-3177.
[7] Wang H,Chen Y,Fernandez-Del Castillo C,et al. Heterogeneity in signaling pathways of gastroenteropancreatic neuroendocrine tumors:a critical look at notch signaling pathway[J]. Mod Pathol,2013,26(1):139-147.
[8] Fujino K,Yasufuku K,Kudoh S,et al. INSM1 is the best marker for the diagnosis of neuroendocrine tumors:comparison with CGA,SYP and CD56[J]. Int J Clin Exp Pathol,2017,10(5):5393-5405.
[9] Rosenbaum J N,Guo Z,Baus R M,et al. INSM1:a novel immunohistochemical and molecular marker for neuroendocrine and neuroepithelial neoplasms[J]. Am J Clin Pathol,2015,144(4):579-591.
[10] Rooper L M,Sharma R,Li Q K,et al. INSM1 demonstrates superior performance ti the individual and combined use of synaptophysin,chromogranin and CD56 for diagnosing neuroendocrine tumors of the thoracic cavity[J]. Am J Surg Pathol,2017,41(11):1561-1569.
[11] Rooper L M,Bishop J A,Westra W H. INSM1 is a sensitive and specific marker of neuroendocrine differentiation in head and neck tumors[J]. Am J Surg Pathol,2018,42(5):665-671.
[12] Tanigawa M,Nakayama M,Taira T,et al. Insulinoma-associated protein(INSM1)is a useful marker for pancreatic neuroendocrine tumor[J]. Med Mol Morphol,2018,51(1):32-40.