KIT exon 11 codon 557/558 deletion/insertion mutations define a subset of gastrointestinal stromal tumors with malignant potential

AIM: To study the association of the frequency and pattern of KIT and PDGFRA mutations and clinicopathological factors in a group of patients with gastrointestinal stromal tumors (GIST). METHODS: Thirty patients with GIST were examined. Exons 9, 11, 13, and 17 of the KIT and exons 12 and 18 of the PDGFRA gene were analyzed for the presence of mutations by PCR amplification and direct sequencing. RESULTS: KIT or PDGFRA mutations were detected in 21 of the 30 patients (70%). Sixteen patients had mutations within KIT exon 11, three within KIT exon 9, and two within PDGFRA exon 18. GISTs with KIT exon 9 mutations were predominantly located in the small intestine, showed a spindle cell phenotype, and were assessed as potentially malignant. GISTs with KIT exon 11 mutations were located in the stomach and intestine, showed mainly a spindle cell phenotype, and were scored as potentially malignant (P < 0.05). Tumors with KIT exon 11 codon 557/558 deletion/insertion mutations were found to be associated with a potentially malignant clinical behaviour (P < 0.003). GISTs with PDGFRA mutations located in stomach showed a mixedcell phenotype and were classified as of very low or low moderate malignant potential. CONCLUSION: Determination of KIT and PDGFRA mutations should be additional parameters for the better prediction of GISTs clinical behaviour. Tumors with deletion/insertion mutations affecting codons 557/558 of the KIT gene seem to represent a distinct subset of malignant GISTs.

KIT-negative gastrointestinal stromal tumors with a long term follow-up:A new subgroup does exist

AIM： To investigate the incidence of KIT immunohostochemical staining in （GI） stromal tumors （GISTs）, and to analyze the clinical manifestations of the tumors and prognostic indicators. METHODS： We retrospectively analyzed 50 cases of previously diagnosed GISTs. Tissue samples were assessed with KIT （CDl17 antigen）, CD34, SMA, desmin, S-100, NSE, PCNA, Ki-67, and BCL-2 for immunohistochemical study and pathological characteristics were analyzed for prognostic factors. RESULTS： Fifteen tumors （30%） were negative in KIT staining. A significant association was observed between gender （male patients： 14/15） and KIT-negative staining （P = 0.003）.The patients＇s mean age was 56.6 years. Tumors developed in stomach （n = 8）, small intestine （n = 5）, large intestine （n = 1） and oesophagus （n = 1）. The mean tumor size was 5.72 cm. The mitotic count ranged from 0-29/50 HPF （mean： 3.4） and 73% of tumors showed no necrosis. The majority of the tumors （67%） had dual or epithelioid differentiation. Tumors were classified as very low or low risk （n = 7）, intermediate risk （n = 5）, and high risk （n = 3） groups. Twelve （80%） patients were alive without evidence of residual tumor for an average period of 40.25 mo （12-82 too）; three patients developed metastatic disease to the liver and eventually died within 2-12 mo （median survival： 8.6 too）.CONCLUSION： A small subgroup of GISTs fulfils the clinical and morphological criteria of these tumors, and lacks KIT expression. These tumors predominantly developed in the stomach, being dual or epithelioid in morphology, which are classified as low risk tumors and presented a better survival status than KIT-positive tumors. The ability to diagnose GISTs still depends on immunohistochemical staining but the research should extend in gene mutations.