title: 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.
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.
authors.affiliation: Department of Pathology, Shizuoka City Shimizu Hospital, Shimizu, Shizuoka, Japan. piyo0111jp@yahoo.co.jp
authors.forename: Tadashi
authors.initials: T
authors.lastname: Terada
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000737:chemistry*; D046152:Gastrointestinal Stromal Tumors / Q000737:chemistry* / Q000196:embryology; D041981:Gastrointestinal Tract / Q000737:chemistry* / Q000196:embryology; D005865:Gestational Age; D006801:Humans; D009130:Muscle, Smooth / Q000737:chemistry* / Q000196:embryology; D032389:Myocytes, Smooth Muscle / Q000737:chemistry; D014411:Neoplastic Stem Cells / Q000737:chemistry; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000032:analysis*
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha
keywords: GI tract; GIST; smooth muscles; stem cell antigens; stem cells