Gastrointestinal stromal tumors may originate from a subset of CD34-positive interstitial cells of Cajal

Most gastrointestinal stromal tumors (GISTs), a subgroup of mesenchymal neo plasms of the gut wall, express both Kit (CD117) and CD34 proteins. It has been suggested that GISTs originate from or differentiate into interstitial cells of Cajal (ICC), after several reports indicated that ICC are likely the only cells in the gut which express both Kit and CD34. ICC are among th e few cell types resident in the gut which express Kit, together with mast cells. However, the question whether or not ICC express CD34 is currently d isputed. Using single-cell reverse transcriptase-polymerase chain reaction (RT-PCR) on cultured murine intestinal cells, single ICC were selected by m orphology and tested for the expression of c-kit and CD34 mRNA Most ICC wer e only c-kit-positive, however a subset (7 out of 43) were double positive for both c-kit and CD34. In the human small intestine, sequential immunohis tochemical staining for Kit and CD34 proteins on the same 3-mu m sections s howed that some of the ICC surrounding Auerbach's plexus and ICC within the circular muscle layer of the small intestine were positive for both Kit an d CD34, In addition, CD34(+)Kit(-) cells were seen adjacent to ICC. These d ata from two different techniques indicate that ICC can be double positive for Kit and CD34, Thus, GISTs with the Kit(+)CD34(+) phenotype may arise fr om a subpopulation of CD34(+) Kit(+) ICC.