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Abstract : |
Gastrointestinal stromal tumors (GIST) are relatively rare solid neoplasms (accounting for about 5% of all soft tissue sarcomas), but still they represent the most common mesenchymal malignancy of the gastrointestinal tract. Until the revolution brought by immunohystology and immunohystochemical laboratory methods, most spindle cell sarcomas of the gastrointestinal tract used to be considered as leyomiomas or leyomiosarcomas, or, occasionally, were regarded as neurogenic tumors. GISTs define a distinct group of digestive tumors that arise from the intestinal cells of Cajal (ICC), also called pacemaker cells, which normally regulate bowel peristalsis. ICC usually express c-Kit (CD117), which is a tyrosinkinase growth factor receptor. This is the best defining feature of GISTs, distinguishing them from true smooth muscle tumors (i.e., leyomiomas and leyomiosarcomas) and tumors arising from neural crest derivates (i.e., schwanomas and neurofibromas); presently, c-Kit immunoreactivity is considered the most specific criterion for the diagnosis of GISTs. Typically, GISTs originate mostly in the stomach (60%) and the small intestine, but may also occur in the rectum (5%), esophagus (2%) and a variety of other sites, including appendix, gallbladder, pancreas, mesentery, omentum, and retroperitoneum (5%). About 5% of all GISTs are metastatic or high-risk tumors at diagnosis. Generally speaking, surgical resection remains currently the mainstay of localized GIST therapy. Imatinib mesylate (Glivecآ®) selectively inhibits the tyrosine-kinase activity of c-Kit and platelet-derived growth factor (PDGF) receptor alpha. In the present, imatinib is indicated as first-line treatment of a metastatic or unresectable malignant GIST. In less than half a decade, GISTs have emerged from historical anonymity to become an important focal point in many trials of targeted therapeutics. The acquisition of a deeper scientific understanding of GISTs became a paradigm for developing new and powerful therapeutic tools in solid tumor oncology. , |
