Your browser doesn't support javascript.
loading
Tyrosine-kinase mutations in c-KIT and PDGFR-alpha genes of imatinib naïve adult patients with gastrointestinal stromal tumours (GISTs) of the stomach and small intestine: relation to tumour-biological risk-profile and long-term outcome
Søreide, K; Sandvik, OM; Søreide, JA; Gudlaugsson, E; Mangseth, K; Haugland, HK.
Afiliação
  • Søreide, K; University of Bergen. Stavanger University Hospital. Stavanger. Norway
  • Sandvik, OM; Stavanger University Hospital. Stavanger. Norway
  • Søreide, JA; University of Bergen. Stavanger University Hospital. Stavanger. Norway
  • Gudlaugsson, E; Stavanger University Hospital. Stavanger. Norway
  • Mangseth, K; Haukeland University Hospital. The Gade Institute. Norway
  • Haugland, HK; Haukeland University Hospital. The Gade Institute. Norway
Clin. transl. oncol. (Print) ; 14(8): 619-629, ago. 2012.
Artigo em Inglês | IBECS | ID: ibc-126959
Biblioteca responsável: ES1.1
Localização: BNCS
ABSTRACT

BACKGROUND:

The identification of activating mutations in either c-KIT cell surface growth factor receptor or platelet-derived growth factor receptor alpha (PDGFRA) has lead the way for the development of novel agents that selectively inhibit key molecular events in gastrointestinal stromal tumour (GIST) pathogenesis. The aim of this study was to investigate the role of c-KIT and PDGFRA gene mutations in primary resectable, imatinib naïve GISTs located in the stomach and small intestine.

METHODS:

All adult patients with GIST located in either stomach or small intestine who underwent surgical resection without prior imatinib (Glivec) treatment were included. DNA extraction and mutational analysis were performed. Mutational analyses were performed for c-KIT (exons 9, 11, 13, and 17) and the PDGFRA genes (exons 12, 14 and 18). Clinical and pathological parameters were analyzed in relation to the mutations in c-KIT and PDGFRA.

RESULTS:

A total of 38 patients who underwent surgery for GIST located in either the stomach (n = 24) or in the small intestines (n = 14) were included. Mutations were found in 31 of 38 (81.6 %) patients, with 24 (63.2 %) located in c-KIT and 7 (18.4 %) in the PDGRFA exons, respectively. Seven patients (18.4 %) were wildtype (WT). The most common mutation was in c-KIT exon 11. Incidentally found GISTs were significantly smaller (size >5 cm in 15 % for incidental vs. 71 % for symptomatic; OR of 13.4, 95 % CI 2.3-76.5; P = 0.001) and had lower mitotic rate (0 % for incidental vs. 44 % of the symptomatic; OR 0.52, 95 % CI 0.36-0.75; P = 0.005). Accordingly, the Fletcher grade was significantly better for incidental cases, with most having very low or low risk (85 %) in contrast to 19 of 25 (76 %) symptomatic cases showing moderate to high-risk features (OR 17.4, 95 % CI 2.98-101.7; P < 0.001). However, the distribution of c-KIT, PDGFRA and WT was not differently distributed between incidental and symptomatic GISTs. Long-term survival up to 25 years (median 8 years) was best determined by Fletcher risk-score in the multivariate model (HR 14.1, 95 % CI 1.7-114.5; p = 0.013).

CONCLUSIONS:

Long-term survival in resected GISTs of the stomach and small intestine is best determined by Fletcher risk-score. Mitotic activity appears related to tumour size and young age at onset. Mutational status did not influence the clinical or tumour-specific features in this cohort (AU)
Assuntos
Buscar no Google
Coleções: Bases de dados nacionais / Espanha Base de dados: IBECS Assunto principal: Piperazinas / Pirimidinas / Neoplasias Gástricas / Benzamidas / Proteínas Proto-Oncogênicas c-kit / Receptor alfa de Fator de Crescimento Derivado de Plaquetas / Tumores do Estroma Gastrointestinal / Neoplasias Intestinais / Antineoplásicos Tipo de estudo: Estudo de etiologia / Estudo prognóstico / Fatores de risco Limite: Adulto / Idoso / Feminino / Humanos / Masculino Idioma: Inglês Revista: Clin. transl. oncol. (Print) Ano de publicação: 2012 Tipo de documento: Artigo Instituição/País de afiliação: Haukeland University Hospital/Norway / Stavanger University Hospital/Norway / University of Bergen/Norway
Buscar no Google
Coleções: Bases de dados nacionais / Espanha Base de dados: IBECS Assunto principal: Piperazinas / Pirimidinas / Neoplasias Gástricas / Benzamidas / Proteínas Proto-Oncogênicas c-kit / Receptor alfa de Fator de Crescimento Derivado de Plaquetas / Tumores do Estroma Gastrointestinal / Neoplasias Intestinais / Antineoplásicos Tipo de estudo: Estudo de etiologia / Estudo prognóstico / Fatores de risco Limite: Adulto / Idoso / Feminino / Humanos / Masculino Idioma: Inglês Revista: Clin. transl. oncol. (Print) Ano de publicação: 2012 Tipo de documento: Artigo Instituição/País de afiliação: Haukeland University Hospital/Norway / Stavanger University Hospital/Norway / University of Bergen/Norway
...