In 2003, Heinrich and colleagues (28) and Hirota and colleagues (29) all found platelet-derived growth factor receptor alpha (PDGFRA) gene mutations as an alternative pathogenesis in GISTs without KIT gene mutation. In January 26, 2006, Sunitinib, a multitargeted TKI with activity against KIT, PDGFR, vascular endothelial growth factor (VEGF) receptor (VEGFR), and FLT-1/KDR, also received FDA approval for the management of patients who are refractory or intolerant to imatinib (30). Overall, about 85% Inhibitors,research,lifescience,medical of GISTs are reported to have activating mutation in KIT or PDGFRA
(28,31,32). CD117 (c-Kit) immunohistochemistry has proven to be a reliable and sensitive diagnostic tool (22,33,34). With the TKI therapies against KIT and PDGFRA (imatinib and sunitinib),
inoperable or metastatic GISTs are now treatable, and a number of additional alternative drugs are in clinical trials. Epidemiology Although the exact incidence of GISTs in the world is hard to determine since the entity Inhibitors,research,lifescience,medical was not uniformly defined until the late 1990s, a Inhibitors,research,lifescience,medical few estimates and studies indicate the incidences of approximately 14.5 cases/million/year in Sweden (35), 14.2 in Northern Italy (36), 13.7 in Taiwan (37), 12.7 in Holland (38), 11 in Iceland (39) and 6.5 in Norway (40). In a recent report, about 5,000 new cases of GISTs were diagnosed annually (41) and a incidence of 6.8/million from 1992 to 2000 (38) in the United States. The overall incidence rates of GIST, therefore, ranges between 6.5 and 14.5 per million per year. In general, little information on the prevalence of GIST was available. Inhibitors,research,lifescience,medical It is believed that the prevalence of GIST is higher, as many patients live with the disease for many years or develop small GISTs only detected at autopsy or if a gastrectomy is performed for other causes (42). A study performed in Germany on consecutive autopsies revealed small (<10 mm) GISTs in 22.5% of individuals who were older than 50 years (43). Rubin and colleagues used the SEER (surveillance, epidemiology, and end results) cancer registry in US for patients with Inhibitors,research,lifescience,medical GIST from 1993-2002 to determine
incidence, prevalence, and 3-year survival and found the overall incidence, prevalence, and 3-year-servival Parvulin rate were 3.2/million, 16.2/million, and 73%, respectively (44). GIST mainly affects middle aged to elderly adults, typically in their 60s (35,45) with no clear gender predilection (46) although some studies demonstrated a Raf inhibitor slight male predominance (39,47). GISTs are uncommonly seen in patients younger than 40, however, cases in children and young adults have been reported (46). The true incidence of GIST in children is unknown. An incidence rate of 0.06/million/year was reported among young adults (20-29 years of age) (37). Other large series studies showed the percentage of patients with GIST below the age of 21 years ranged from 0.5% to 2.7% (45,46,48).