**3. Molecular biology**

per 100,000 in 1992 to 0.688 cases per 100,000 in 2002, which is a 25-fold increase in incidence. This increase occurred after the availability of diagnostic criteria, especially after the year 2000 [7]. In 1992, 93% of mesenchymal tumors of GIT were identified as smooth muscle neoplasm and 6% as GISTs. In 1995, Miettinen et al. [8] discovered that 70% of GIST are positive for CD34, a myeloid progenitor cell antigen. Furthermore, CD34 were also found in Schwann cell tumors and some smooth muscle tumors [6]. In the late 1990s, Hirota et al. [9] discovered that GIST expresses KIT (CD117), a receptor tyrosine kinase encoded by the proto-oncogene c-kit. Subsequent studies showed that mutations in c-KIT are present in 85–100% of GIST cases, but not in leiomyomas or leiomyosarcomas. These findings made a breakthrough in identifications and management of GISTs. In the SEER data published by Perez et al. [7], 82% of mesenchymal tumors of GIST were classified as GIST and 17% were classified as smooth muscle neoplasms in 2002, which shows how GISTs were poorly identified and were underdiagnosed [7]. GISTs appear to be more common in African Americans, Asians, and Pacific Islanders than in Caucasian patients, and men appear to have a slightly increased incidence [7, 10]. GISTs tend to be infrequent before the age of 30 and are most common after the age of 60 [7]. The median age of diagnosis is between 58 and 65 years [7, 10–13]. Two studies from

Europe have shown that GIST incidence is about 1.1 cases/100,000/year [11, 14].

Though rare, GISTs can also affect the pediatric population. A study carried out by Miettinen et al. which included 1782 patients with gastric GIST, reported 44 cases under the age of 21 (2.6%) [15] with an age range from 5 to 21 and a median age of 14.5 years [15]. Prakash et al. [16] reported six cases of gastric GIST with a mean age of 12.8 and an age range from 10 to 18. Pediatric GISTs are commonly of epithelioid type, occur more in females, and have a higher incidence of multifocal presentation and lymph node metastasis. Pediatric GISTs also tend to

There are no known risk factors for GIST. Though most of GISTs are sporadic, the minority

Familial GIST syndrome: several family members with hereditary mutations in either the KIR or PDGFRA genes have been reported in the study [19–28]. These families have a higher risk to develop multiple gastric and small bowel GISTs. Some patients may have skin hyperpigmentation, dysphagia, gastrointestinal autonomic nerve tumors, intestinal fibromatosis, and

Carney-Stratakis syndrome is an autosomal-dominant disease which is characterized by dyad of multifocal GISTs and paragangliomas [29]. Patients do not have KIT or PDGFRA mutations, but do have mutations of succinate dehydrogenase subunits (SDH) A, B, C, or D [30]. Carney's triad: a very rare non-heritable syndrome characterized by gastric GIST, paraganglioma and pulmonary chondromas. These patients are characterized by mutations succinate

dehydrogenase subunit (SDH) C [29] but lack mutations of KIT and PDGFRA.

lack a KIT or a platelet-derived growth factor receptor-α (PDGFRA) mutation [17, 18].

**2. Risk factors**

70 Gastric Cancer - An Update

occur as part of hereditary syndrome.

inflammatory fibroid polyps [19–28].

GISTs are characterized by mutations in KIT and PDGFRA genes that encode tyrosine kinase receptor type III [32].
