title: Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal.
abstract: The interstitial cells of Cajal (ICC) form a complex cell network within the gastrointestinal tract wall where they function as a pacemaker system. Expression of the kit proto-oncogene is essential for the development of this system. The aim of our study was to examine the hypothesis that gastrointestinal stromal tumors differentiate toward cells with an ICC phenotype. Ultrastructurally, 58 stromal tumors were characterized and found to share many features with ICC. Seventy-eight stromal tumors were immunophenotyped, particularly with regard to the kit receptor. All 78 tumors revealed strong, homogeneous immunoreactivity for the kit receptor as did ICC of adjacent and control gastrointestinal walls. Focal hyperplasia and hypertrophy of kit receptor positive cells were also observed in the gastrointestinal wall adjacent to the tumors. CD34 immunoreactivity observed in interstitial cells surrounding Auerbach's ganglia suggests that a subpopulation of ICC is CD34 positive and may explain why 56 of 78 stromal tumors were CD34 positive. Thirty control tumors, including gastrointestinal leiomyomas and leiomyosarcomas, were all negative for the kit receptor. We conclude that gastrointestinal stromal tumors show striking morphological and immunophenotypic similarities with ICC and that they may originate from stem cells that differentiate toward a pacemaker cell phenotype. We propose that the noncommittal name "gastrointestinal stromal tumor" be replaced by gastrointestinal pacemaker cell tumor.
authors.affiliation: Department of Pathology, Gothenburg Musculoskeletal Tumor Center, University of Gothenburg, Sahlgrenska University Hospital, Sweden.
authors.forename: L G
authors.initials: LG
authors.lastname: Kindblom
authors.forename: H E
authors.initials: HE
authors.lastname: Remotti
authors.forename: F
authors.initials: F
authors.lastname: Aldenborg
authors.forename: J M
authors.initials: JM
authors.lastname: Meis-Kindblom
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015388:Organelles / Q000648:ultrastructure; D010641:Phenotype; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D018952:Antigens, CD34; D016326:Extracellular Matrix Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit