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exon11 突变、Ki67 和 p16(INK4A) 作为 GIST 患者预后的预测因子。

Exon 11 mutations, Ki67, and p16(INK4A) as predictors of prognosis in patients with GIST.

机构信息

Programa de Pós-Graduação: Ciências em Gastroenterologia e Hepatologia, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

出版信息

Pathol Res Pract. 2011 Nov 15;207(11):701-6. doi: 10.1016/j.prp.2011.09.008. Epub 2011 Oct 24.

DOI:10.1016/j.prp.2011.09.008
PMID:22024151
Abstract

Prognostic biomarkers for GIST are under investigation. The aim of this study was to assess whether exon 11 mutations, Ki67, and p16(INK4A) are predictors of prognosis in GIST. Consecutive GIST cases (n=84) had their specimens evaluated for exon 11 mutations and expression of Ki67 and p16(INK4A). 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 p16(INK4A). 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 p16(INK4A) need further studies to address the prognostic value.

摘要

用于 GIST 的预后生物标志物正在研究中。本研究旨在评估外显子 11 突变、Ki67 和 p16(INK4A)是否可预测 GIST 的预后。对连续的 GIST 病例(n=84)进行了外显子 11 突变和 Ki67 和 p16(INK4A)表达的评估。手术病例根据 NIH 和 Miettinen 分类进行分类,并从医院数据库分析生存情况。GIST 主要位于胃(45%)和梭形细胞形态(74%)。风险类别非常低或低为 28%,中间为 23%,高为 49%。在研究的 60 例病例中,有 29 例(48%)发现外显子 11 突变。有 12 个点突变,10 个缺失,4 个重复,3 个双突变。三分之一的 GIST 具有高 Ki67 指数(>3%)或 p16(INK4A)阴性。多变量分析显示,死亡率的独立预测因子是 Ki67>3%(HR=7.3;P=0.036)和高有丝分裂指数(HR=10.4;P=0.043)。外显子 11 突变与生存之间没有关联。本研究表明,Ki67>3%是 GIST 患者预后不良的独立预测因子。外显子 11 突变和 p16(INK4A)阴性需要进一步研究以确定其预后价值。

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