INSM1 Expression In Mesenchymal Tumors And Its Clinicopathological Significance

Background: Insulinoma-associated protein 1(INSM1),a transcription regulator with five zinc-finger DNA binding domains and several potential functional domains,was isolated by Goto et al.in 1992 from the c DNA library of human insulinoma subtracted gene.It has been identified as a nuclear marker of neuroendocrine tumors.In addition to high expression in the neural endocrine system of the early embryo,it is also expressed in the digestive/head and neck/skin/prostate/female genital tract/ neuroendocrine tumors,pheochromocytoma,pituitary adenoma,medullary thyroid carcinoma.INSM1 is not expressed in normal adult tissue or in most non-neuroendocrine tumors.It regulates a variety of downstream signaling pathways,including Sonic Hedgehog,PI3K/Akt,MEK/ERK1/2,ADK,p53,Wnt,histone acetylation,LSD1,cycline d 1,ASCL1 and N-Myc.Although INSM1 appears to be a subtle and specific biomarker for neuroendocrine tumor,its expression in mesenchymal tumors and its clinicopathological significance remain unclear.Objective: 1.To observe the expression of INSM1 in mesenchymal tumors 2.To find the diagnostic significance of INSM 1 in mesenchymal tumors 3.To explore the pathogenesis of INSM1 in mesenchymal tumorsMethods: Three pathologists in the pathology department of Tongji Hospital initially reexamined and selected sections of 576 cases from 2017 to 2021.After HE staining and INSM1 immunohistochemical staining,the expression of INSM1 in mesenchymal tumors was evaluated by the three pathologists.At the same time,the level of INSM1 m RNA was analayzed in mesenchymal tumor by GEPIA(A tool of exploration for TCGA database)and R language(A tool of exploration for GEO database).T test was used to compare the data of the two groups.Chi-square test or Fisher test was used for immunohistochemical data(P <0.05).Results: 1.At transcription level,GEO data suggested that INSM1 expression of AITL/ALCL was significantly higher/lower than their normal controls.INSM1 expression of AITL was significant higher than lymphoblastic lymphoma,lymphocyte lymphoma,diffuse large B cell lymphoma,follicular lymphoma,Burkitt lymphoma,marginal zone lymphoma,mantle cell lymphoma,Hodgkin’s lymphoma,plasma cell lymphoma,and ALCL.Well-differentiated liposarcoma(WDLPS)was significant higher than normal fat(P =0.014)/dedifferentiated liposarcoma(DDLPS)(P=0.0248).Undifferentiated sarcoma was lower than rhabdomyosarcoma(P=0.0176)2.The positive rate of AITL was 18/48(47.4%),Plasmoblastic lymphoma 2/4(50%),dedifferentiated liposarcoma 9/20(45%),solitary fibrous tumor 4/9(44.4%),and 3/6(50%)chondrosarcoma.3.AITL was significantly higher than Hodgkin’s lymphoma lymphoma(P = 0.008),T/B lymphoma(P = 0.001),lymphocyte lymphoma(P = 0.001),mantle cell lymphoma(P = 0.003),NK/T cell lymphoma(P = 0.031)and anaplastic large cell lymphoma(P = 0.004)at protein level.4.At INSM1 protein level: WDLPS was significantly lower than DDLPS(P = 0.015),undifferentiated sarcoma and rhabdomyosarcoma(P = 0.007),both groups showed significant difference.The positive rate of INSM1 was 44.4% in solitary fibrous tumor,but0 in protuberant cutaneous fibrosarcoma.The INSM1 protein level of the two tumors was significantly different(P = 0.004).Conclusion: 1.The combination of GEO data and immunohistochemistry data indicated that the expression level of INSM1 was higher in AITL compared with normal control,suggesting that INSM1 may be involved in pathogenesis of AITL.2.The abnormal expression of INSM1 was found in WDLPS according to bioinformatics and immunohistochemistry analysis,and the positive rate of INSM1 was higher in DDLPS than in WDLPS.INSM1 may be involved in the regulation of liposarcoma differentiation.3.GEO and immunohistochemical analysis showed that there were significant differences in the expression of INSM1 between AITL and Hodgkin’s lymphoma,undifferentiated sarcoma and rhabdomyosarcoma,WDLPS and DDLPS,SFT and dermatofibrosarcoma protuberans.These findings may assist in the differential diagnosis of these tumors when common markers are difficult to identify,enriching the diagnostic index system of mesenchymal tumors.