Dr Jonathan Fletcher explains at ESMO 2016 how microGISTS differ from malignant GIST. See link here.
MicroGISTs (small gastric GISTs less than 2 cm with VERY low mitotic rates) are surprisingly common in the general older adult population, with some 25% of older adults having them. These are considered truly benign but with the important caveat that we must consider whether a small gastric mass is a true microGIST and not a malignant one which happened to be caught very early.
MicroGISTs lack certain molecular characteristics which constrain their size and invasiveness. However, microGISTs do carry the same KIT mutations as are found in highly malignant GISTs, including some of the “bad” mutations (such as exon 11 deletion) associated with a worse prognosis in malignant GIST. The observations about KIT mutants in microGISTs indicates that activating KIT mutations are not by themselves sufficient for high malignancy.
So what do miroGISTs lack molecularly that constrains their malignant potential?
Dr Fletcher says:
1) microGISTs require the growth factor ‘stem cell factor’ (SCF) provided by ancillary smooth muscle cells within the tumor mass. Malignant GISTs no longer require SCF provided by other cells. SCF is the growth factor which activates normal KIT.
2) microGISTs lack genomic instability, (the rapid accumulation of additional random DNA abnormalities that lead to drug resistance in malignant GIST)
3) microGISTs lack additional DNA abnormalities outside of the abnormalities of KIT and PDGFRA, needed to fully uncontrollable cell growth.
You can click icons on the right side to see a PDF of the slides, or to watch his video.