RESUMO
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the digestive tract. Inherent overexpression of receptor tyrosine kinase KIT (CD117) and mutations in c-Kit or PDGFRA genes are highly significant prognosticators. A first Russian investigation of c-Kit and PDGFRA mutations in GIST was carried out in 60 patients. c-Kit mutations were identified in 83.3% (50/60), the most frequent being mutations in c-Kit exon 11 (73.4%, 44/60). Among them, different mutations were identified in the 5'-end of c-Kit exon 11 in 37 GISTs. Duplications in the 3'-end of c-Kit exon 11 were reported in 7 tumors. Mutations in c-Kit exon 9 (73.4%, 44/60) were found in 5 tumors (8.3 3%, 5/60) while mutations in c-Kit exon 13 (0%, 44/60) and 17 (1.7%, 1/60) were rare. PDGFRA mutations in exon 18 were identified in (8.3 3%, 5/60). Substitution D842V occurred only in one gastric epithelioid-cell GIST. The remaining PDGFRA mutations contained deletions with aminoacids 842-846. There were no c-Kit and PDGFRA mutations in five tumors. Our findings point to a significant correlation between c-Kit and PDGFRA mutations, on the one hand, and tumor site and histological pattern, on the other. Hence, c-Kit and PDGFRA mutation detection should be used as an additional prognosticator for efficacy of target therapy.
Assuntos
Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Mutação , Proteínas Proto-Oncogênicas c-kit/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , PrognósticoRESUMO
Stromal tumors are singled out from smooth muscle and neurogenic neoplasms into a special group due to differences in CD117 expression caused by mutation of c-kit gene. Out of 57 stromal tumors, 37 (64,9%) located in the stomach, 17 (29,8%) in the small intestine and 3 (5,3%) in the colon. Immunohistochemically, all the tumors expressed CD117 and vimentine. Smooth muscle actin was found in 82% tumors, S-100 protein in 75%, neuron-specific enolase in 66% cases. Malignant tumors were in 93% cases, and in 7% benign. Metastases were observed in 47.7% cases, recurrences in 14%. The liver was most frequent site of metastases (88.9%), peritoneum (51.9%). 21% patients died of progression of the underlying disease during the follow-up of 6-60 months.
