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胚胎肠道的平滑肌和干细胞表达KIT、PDGFRRA、CD34以及许多其他干细胞抗原:提示胃肠道间质瘤起源于平滑肌和肠道干细胞。

Smooth muscles and stem cells of embryonic guts express KIT, PDGFRRA, CD34 and many other stem cell antigens: suggestion that GIST arise from smooth muscles and gut stem cells.

作者信息

Terada Tadashi

机构信息

Department of Pathology, Shizuoka City Shimizu Hospital, Shimizu, Shizuoka, Japan.

出版信息

Int J Clin Exp Pathol. 2013 May 15;6(6):1038-45. Print 2013.

PMID:23696920
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3657355/
Abstract

Gastrointestinal stromal tumor (GIST) is believed to original from interstitial cells of (ICC) present in Auerbach's nerve plexus. GIST frequently shows gain-of-function mutations of KIT and PDGFRA. In practical pathology, GIST is diagnosed by positive immunostaining or KIT and/or CD34. The author herein demonstrates that human embryonic gastrointestinal tract smooth muscles (HEGITSM) and human embryonic stem gastrointestinal cells (HEGISC) consistently express KIT, CD34, NCAM, PDGFRA and other stem cell (SC) antigens NSE, synaptophysin, chromogranin, bcl-2, ErbB, and MET throughout the embryonic development of 7-40 gestational week (GW). CK14 was negative. The author examines 42 cases (7-40 GW) of embryonic GI tract (EGI). The HEGISM, HEGIST, and gall bladder smooth muscles (SM) were consistently positive for KIT, CD34, NCAM, PDGFRA, synaptophysin, chromogranin, NSE, bcl-2, ErbB2, and MET in foregut, stomach, GB, midgut, and hindgut throughout the fetal life (7-40 GW). The stem cells (SC) were seen to create the SM, nerves, ICC, and other all structures of GI tract. In adult gastrointestinal walls (n=30), KIT, CD34, PDGFRA, and S100 proteins were expressed in Auerbach's nerve plexus and ICC. The bronchial and vascular SM of embryos did not express these molecules. In GIST, frequent expressions of KIT (100%, 30/30), CD34 (90%, 27/30), and PDGFRA (83%, 25/30) were seen. In general, characteristics of tumors recapitulate their embryonic life. Therefore, it is strongly suggested that GIST may be originated from GI SM and/or GI SC in addition to ICC.

摘要

胃肠道间质瘤(GIST)被认为起源于奥尔巴赫神经丛中的间质细胞(ICC)。GIST常表现为KIT和PDGFRA的功能获得性突变。在实际病理学中,GIST通过KIT和/或CD34的免疫染色阳性来诊断。本文作者证明,在妊娠7至40周(GW)的整个胚胎发育过程中,人类胚胎胃肠道平滑肌(HEGITSM)和人类胚胎干细胞胃肠道细胞(HEGISC)持续表达KIT、CD34、NCAM、PDGFRA以及其他干细胞(SC)抗原NSE、突触素、嗜铬粒蛋白、bcl-2、ErbB和MET。细胞角蛋白14(CK14)呈阴性。作者检查了42例(7至40 GW)胚胎胃肠道(EGI)。在胎儿期(7至40 GW)的前肠、胃、胆囊、中肠和后肠中,HEGISM、HEGIST和胆囊平滑肌(SM)的KIT、CD34、NCAM、PDGFRA、突触素、嗜铬粒蛋白、NSE、bcl-2、ErbB2和MET始终呈阳性。可见干细胞(SC)形成了胃肠道的平滑肌、神经、ICC以及其他所有结构。在成人胃肠道壁(n = 30)中,KIT、CD34、PDGFRA和S100蛋白在奥尔巴赫神经丛和ICC中表达。胚胎的支气管和血管平滑肌不表达这些分子。在GIST中,可见KIT(100%,30/30)、CD34(90%,27/30)和PDGFRA(83%,25/30)的频繁表达。一般来说,肿瘤的特征重现其胚胎期。因此,强烈提示GIST除了起源于ICC外,还可能起源于胃肠道平滑肌和/或胃肠道干细胞。

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