The reappraisal of gastrointestinal stromal tumors: from Stout to the KIT revolution

Abstract

For five decades gastrointestinal stromal tumors (GISTs) truly have represented one of the most confusing as well as neglected areas of both surgical pathology and clinical oncology. The recognition of the central role played by KIT expression in the development of the interstitial cell of Cajal and of the activating KIT mutations in the pathogenesis of GIST have been the keys for a more precise categorization of this long elusive clinicopathological entity. A Consensus Conference held at the National Institutes of Health in 2001 provided both an evidence-based definition and a practical scheme for the assessment of the risk of aggressive clinical behavior. This scheme is based on evaluation of the size and mitotic rate of the tumors, and its use is strongly advocated. On the basis of current data GISTs can be defined as a distinctive group of KIT-expressing mesenchymal neoplasms of the gastrointestinal tract, showing differentiation towards the interstitial cell of Cajal, also known as the gastrointestinal pacemaker cells. Metastatic GISTs have been a virtually incurable disease until the elucidation of the role of KIT mutations. STI-571 (imatinib mesylate) is a molecule that inhibits the function of various receptors with tyrosine kinase activity, such as abl, the bcr-abl chimeric product, platelet-derived growth factor receptor, and KIT. Following its successful use in the treatment of chronic myeloid leukemia, STI-571 has also proved extremely effective in targeting metastatic GIST. Data regarding the duration of the response to this therapy are not yet available, and therefore any overenthusiasm should be avoided. Nonetheless, the GIST story remains paradigmatic of a totally innovative approach to cancer therapy which until now is the most elegant translation of cancer biology experimental knowledge into clinical practice.

Prognostic value of NFκB, CD9, and VEGF in gastrointestinal stromal tumors

“…GISTs most commonly occur in the stomach and small intestine [10, 11]. In this study, more cases were located in the stomach and small intestine in accordance with the literature (stomach localization is 43% (15/35), for small bowel it is 34% (12/35)).…”

“…They appear everywhere from the esophagus to the rectum, but most commonly they occur in the stomach and small intestine [10, 11]. 60–70% occur in the stomach, 25–35% in the small intestine, 5% in the colon, rectum or appendix, and 2–3% in the esophagus [1, 11, 12].…”

Retrospective analysis of prognostic factors affecting the recurrence and disease-free survival following surgical management of gastrointestinal stromal tumors

“…Miettinen et al have demonstrated that spindle cell histology of GIST presents poor prognosis (21). Furthermore, lower cellularity has been described as a useful prognostic factor, while severe nuclear atypia has been mostly seen in aggressive tumors (23,24). In our study, cell type, cellularity, and nuclear pleomorphism had no statistically significant effect on recurrence.…”

Gastrointestinal stromal tumor: 15-years’ experience in a single center

“…Advance in pathology, immunohistochemistry and molecular biology in recent years has greatly improved the diagnosis of GIST. It is now considered that GISTs arise from interstitial Cajal cells (ICCs), expressing CD117 (product of c-kit proto-oncogene), and harboring c-kit or platelet-derived growth factor receptor alpha (PDGFRA) gain-of-function mutation [ 3 – 5 ].…”