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胃肠道间质瘤胰岛素样生长因子1受体表达水平与伊马替尼耐药的相关性

Correlation between the expression of insulin like growth factor 1 receptor in gastrointestinal stromal tumors and imatinib mesylate resistance

  • 摘要:
    目的 探讨胃肠道间质瘤(gastrointestinal stromal tumor,GIST)中胰岛素样生长因子1受体(insulin-like growth factor 1 receptor,IGF1R)的表达与伊马替尼(imatinib mesylate,IM)耐药的关系。
    方法 回顾性分析2008年1月至2014年1月复旦大学附属中山医院普通外科收治的134例GIST患者的临床资料,其中IM耐药26例,非耐药108例。将所有患者术后病理标本制成组织芯片。采用免疫组化法检测组织芯片中IGF1R蛋白表达水平,并分析不同临床病理特征组间IGF1R表达差异。采用Kaplan-Meier绘制生存曲线,对IM耐药患者进行分析。
    结果 GIST组织IGF1R高表达组与低表达组间性别、年龄、肿瘤大小、原发部位、核分裂相、突变基因、美国国立卫生研究院(NIH)危险度分级差异均无统计学意义。IM耐药患者GIST组织IGF1R的表达率(73.08%)高于非耐药患者(41.67%),差异有统计学意义(χ2=8.286,P=0.004)。IM耐药患者的生存分析显示,IGF1R高表达病例总生存时间(overall survival,OS)显著低于IGF1R低表达患者(35.3 vs 71.3个月),差异有统计意义(P=0.04)。
    结论 IGF1R可能参与GIST患者IM耐药,IM耐药患者IGF1R高表达可作为不良预后指标。

     

    Abstract:
    Objective To explore the expression of insulin-like growth factor 1 receptor (IGF1R) in the gastrointestinal stromal tumor (GIST) and its clinical significance.
    Methods Clinical data of 134 GIST patients underwent operations at the Department of General Surgery at Zhongshan Hospital, Fudan University between January 2008 and January 2014 were retrospectively analyzed, including IM resistant group (n=26) and non-resistant group (n=108). The clinicopathological data were collected and immunohistochemical analysis was performed based on tissue microarray to estimate the expression of IGF1R. Pearson χ2 test was used to analyze the difference in IGF1R protein expression among groups with different clinicopathological characteristics. Survival curves were estimated using the Kaplan-Meier method and were compared using the log-rank test.
    Results There were no significant differences in gender, age, tumor size, primary site, mitotic phase, mutation gene and NIH risk classification between IGF1R high expression group and low expression group. The expression rate of IGF1R protein in IM-resistant GIST tissues was 73.08%, and that in non-resistant tissues was 41.67%. The difference between the two groups was statistically significant (χ2=8.286, P=0.004). Univariate survival analysis of 26 cases with IM resistance showed that patients with high IGF1R expression had a significantly lower OS than those with low IGF1R expression (35.3 vs 71.3 months, P= 0.04).
    Conclusions High expression of IGF1R may be involved in the mechanism of IM resistance in GIST and can serve as an indicator of poor prognosis in IM resistant cases.

     

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