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Exon 11 mutations, Ki67, and p16(INK4A) as predictors of prognosis in patients with GIST |
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| Authors: | Cerski Marcelle R Pereira Fernanda Matte Ursula S Oliveira Francine H Crusius Felipe L Waengertner Luiz E Osvaldt Alessandro Fornari Fernando Meurer Luise |
| Institution: | a Programa de Pós-Graduação: Ciências em Gastroenterologia e Hepatologia, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil b Programa de Pós-Graduação em Cirurgia, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil c Programa de Pós-Graduação em Genética e Biologia Molecular, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil d Programa de Pós-Graduação em Saúde da Infância e Adolescência, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil e Departamento de Patologia, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil f Serviço de Patologia, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil g Serviço de Cirurgia, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil h Centro de Terapia Gênica, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil |
| Abstract: | Prognostic biomarkers for GIST are under investigation. The aim of this study was to assess whether exon 11 mutations, Ki67, and p16INK4A are predictors of prognosis in GIST. Consecutive GIST cases (n = 84) had their specimens evaluated for exon 11 mutations and expression of Ki67 and p16INK4A. Surgical cases were categorized according to NIH and Miettinen's classification, and survival was analyzed from hospital database. GISTs were predominately gastric (45%) and with spindle cell morphology (74%). The risk category was very low or low in 28%, intermediate in 23%, and high in 49%. Exon 11 mutation was identified in 29 (48%) out of 60 cases studied. There were 12 point mutations, 10 deletions, 4 duplications, and 3 double mutations. A third of GISTs had either high Ki67 index (>3%) or negativity for p16INK4A. In multivariate analysis, independent predictors of mortality were Ki67 > 3% (HR = 7.3; P = 0.036) and high mitotic index (HR = 10.4; P = 0.043). There was no association between exon 11 mutations and survival. This study suggests that Ki67 > 3% is an independent predictor of poor prognosis in patients with GIST. Exon 11 mutations and negativity for p16INK4A need further studies to address the prognostic value. |
| Keywords: | Gastrointestinal stromal tumors Biological markers Antigen Ki67 p16INK4A Exons |
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