Mutation Analysis of Genes Related to Gastrointestinal Stromal Tumors

PURPOSE: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the gastrointestinal tract. Recent studies have revealed much of the biological and genetics underpinning GISTs. METHODS: KIT, PDGFRA, NF2 and GPHN mutations were examined by PCR-SSCP and DNA sequencing. Immunohistochemical analyses of CD117, CD34, SMA, S-100 and desmin were performed in 11 GISTs cases, and each tumor classified as being either very low, low, intermediate or high risk. RESULTS: Mutation in exon 11 of KIT was identified in 6 of the 11 GISTs, but mutations in exon 9, 13 and 17 of KIT were not detected. Three cases lacking KIT mutations showed PDGFRA mutations. No NF2 mutations were detected. GPHN gene mutation in exon 1 was identified in one case, which showed a simple point mutation in exon 11 of KIT. In a correlation between the mutation types and risk of aggressive behavior, four tumors involved multiple ( >2 codons) KIT mutations and one showed a point mutation of KIT plus a GPHN mutation were high risk, but one tumor with a point mutation of KIT showed a low risk. Three tumors having a PDGFRA mutation were of intermediate or very low risk. CONCLUSION: Mutations at exon 9, 13 or 17 of KIT and a NF2 mutation are considered rare in sporadic GIST. KIT and PDGFRA mutations appeared to be alternatives. A GPHN mutation occurring with a KIT mutation may be a secondary change in the pathogenesis of GIST, as the KIT mutation is a major event in GIST. KIT mutant GIST may have a poorer prognosis than PDGFRA mutant GIST.

Preoperative Predictive Factors of Lymph Node Metastasis in Early Gastric Cancer

PURPOSE: Early gastric cancer (EGC) is defined as gastric cancer confined to the mucosa or submucosa, regardless of lymph node (LN) metastasis. LN metastasis is the most important factor in the treatment of EGC. If LN metastasis is predicted before or during surgery, function preserving surgery, such as endoscopic mucosal resection, laparoscopic partial gastrectomy, and pylorus preserving gastrectomy, without radical LN dissection, can be applied. This study was undertaken to determine the factors affecting LN metastasis and to aid in planning therapeutic approaches for such patients. METHODS: A retrospective study was performed on 1, 203 patients with EGC, who had undergoing a gastrectomy, with lymphadectomy, between 1990 and 2003 at the Keimyung University, Dongsan Medical Center. We analyzed tumor size, depth of invasion, macroscopic, and histologic types and lymph node metastasis using preoperative endoscopy and radiological findings. RESULTS: The incidence of EGC of all gastric cancer has increased annually. Of the 1, 203 patients, 54.2% and 45.8% had mucosal and submucosal cancers, respectively. The incidences of LN metastasis were 4.0% and 23.0% in mucosal and submucosal cancers, respectively. There was no LN metastasis in mucosal cancer, with a tumor size of less than 1 cm (0/169). In the elevated and flat types, the size of the tumors were between 1 and 2 cm, and there was no LN metastasis (0/40), (0/28), but with the depressed type there was an LN metastasis rate of 6.1%. In the well differentiated type, there were 0.5 (1/193) and 12.9% (11/85) LN metastasis in the mucosal and submucosal cancers, respectively. CONCLUSION: A gastrectomy without LN dissection can be applied for EGC less than 1 cm in size and to all well differentiated types of mucosal cancer. Also, it can be applied to elevated and flat EGC types less than 2 and 1 cm in size in mucosal cancer and less than 1 cm sized in submucosal cancers, respectively. A conventional gastrectomy, with LN dissection, is recommended in other EGC types.