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Annals of Oncology 2007 18(Supplement 6):vi136-vi140; doi:10.1093/annonc/mdm243
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© 2007 European Society for Medical Oncology

gastro-intestinal cancer

Gastrointestinal stromal tumors (GISTs): focus on histopathological diagnosis and biomolecular features

G Badalamenti1, V Rodolico2, F Fulfaro1, S Cascio1, C Cipolla3, G Cicero1, L Incorvaia1, M Sanfilippo1, C Intrivici1, L Sandonato3, G Pantuso3, MA Latteri3, N Gebbia1 and A Russo1,*

1 Section of Medical Oncology
2 Section of Pathology
3 Section of Surgical Oncology, Department of Surgical and Oncology, Università di Palermo, Palermo, Italy

* Correspondence to: Antonio Russo, MD Section of Medical Oncology, Department of Oncology, School of Medicine, Università di Palermo, Via del Vespro 127, 90127 Palermo, Italy. Tel: +39-091-6552500; Fax: +39-091-6554529; E-mail: lab-oncobiologia{at}usa.net

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract that are believed to originate from a neoplastic transformation of the intestinal pacemaker cells (interstitial cells of Cajal) normally found in the bowel wall or their precursors. Although the microscopic features have been known for a long time, the defining characteristic of GIST is the presence of the cell-surface antigen CD117 (KIT), which is demonstrated by immunohistochemistry. KIT, which is a growth factor transmembrane receptor, is the product of the proto-oncogene c-kit (chromosome 4). Surgical removal remains the only curative treatment for patients with GISTs. Tumor size, mitotic index, anatomic location, tumor rupture and disease-free interval are the classic characteristics used to predict the clinical course of patients who undergo complete gross resection.

Most GISTs express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. Imatinib mesylate is a rationally designed, molecularly specific oral anticancer agent that selectively inhibits several protein tyrosine kinases central to the pathogenesis of human cancer and which has demonstrated remarkable clinical efficacy in patients with chronic myeloid leukemia and malignant GISTs. More recently Sunitinib, a new KIT/PDGFRA kinase inhibitor, has been tested in patients with GIST resistant to imatinib, with promising results.

Key words: gastrointestinal stromal tumors, histopathological diagnosis, molecular biology, novel therapies


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