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Biology, diagnosis and therapeutic options in gastrointestinal stromal tumours.

Gastrointestinal stromal tumours (GIST) are the most common form of mesenchymal tumour of the intestinal tract. The incidence in Italy is approximately 800-1,400 new cases/year; the most common localization is the stomach (50-60%), small bowel (20-30%), rectum (10%) and esophagus (5%). Extra-abdominal localizations are very rare. GIST characteristically express the Kit protein, a transmembrane tyrosine kinase receptor for the specific ligand. Most GIST have a mutation in kit receptor which becomes constitutive for the neoplasm. Kit mutation is a early tumorogenesis event. The disease clinically can present as an occasionally finding or can be diagnosed after hemorrhage, perforation or obstruction of the gastrointestinal tract. Surgery is the mainstay of the therapy mainly in primary tumour. More debated is its role in metastatic disease. In this situation imatinib mesilate, a tyrosine kinase inhibitor, is the drug of choice which has changed the natural history of the disease. Metastatic GIST before imatinib mesilate discovery had 6 months survival, now in the 3 published studies after 3 years of follow-up, median survival has not already reached. New drugs are now under evaluation in order to prolong the pharmacological activity of tyrosine kinase inhibition after progression of the disease.