Expression of HSP90 in gastrointestinal stromal tumours and mesenchymal tumours
Expression of HSP90 in gastrointestinal stromal tumours and mesenchymal tumours
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DOI：
10.1111/j.1365-2559.2010.03550.x
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发表时间：
2010-05-01
期刊：
影响因子：
6.4
通讯作者：
Kim, Sung
中科院分区：
文献类型：
--
作者：
Kang, Gu Hyun;Lee, Eui Jin;Kim, Sung
目的：热休克蛋白（HSP）在包括癌症在内的应激增加的条件下上调。最近，HSP90已被证明对KIT癌蛋白的表达和激活至关重要。目的是探讨HSP90表达在胃肠道间质肿瘤（gist）和其他间质肿瘤中作为预后标志物和治疗靶点的作用。方法与结果：应用免疫组化方法对92例胃肠道间质瘤、47例肠系膜纤维瘤、6例神经鞘瘤、平滑肌瘤、黑色素瘤、恶性周围神经鞘瘤和平滑肌肉瘤组织中HSP90的表达进行检测。选取22例进行免疫印迹检测。33.7%的gist患者存在HSP90过表达，并与非胃部位、混合组织学亚型、高有丝分裂指数、高风险等级和特定突变基因型相关。在间质肿瘤中，HSP90在66.7%的恶性周围神经鞘肿瘤、83.3%的平滑肌肉瘤和100%的黑色素瘤中过表达。免疫印迹法检测HSP90表达与免疫组化结果相关。Cox比例风险模型显示，HSP90表达是gist复发的独立预测因子（P = 0.003）。结论：HSP90的过表达可预测胃肠道间质瘤的不良行为，并可能为伊马替尼耐药的胃肠道间质瘤和其他间质肉瘤提供治疗方案。
Aims:Heat shock proteins (HSP) are up-regulated under conditions of increased stress, including cancer. Recently, HSP90 has been shown to be crucial to the expression and activation of the KIT oncoprotein. The aim was to explore the role of HSP90 expression as a prognostic marker and therapeutic target in gastrointestinal stromal tumours (GISTs) and other mesenchymal tumours.Methods and results:The expression of HSP90 was evaluated by immunohistochemistry in 92 GISTs, 47 mesenteric fibromatoses, six schwannomas, leiomyomas, melanomas, malignant peripheral nerve sheath tumours and leiomyosarcomas. Western blotting was performed in 22 selected cases. HSP90 overexpression was found in 33.7% of GISTs and was correlated with non-gastric location, mixed histological subtype, high mitotic index, high risk grades, and specific mutation genotypes. In mesenchymal tumours, HSP90 overexpression was found in 66.7% of malignant peripheral nerve sheath tumours, 83.3% of leiomyosarcomas, and 100% of melanomas. HSP90 expression by Western blotting correlated with the results of immunohistochemistry. The Cox proportional hazards model showed that HSP90 expression is an independent predictor of recurrence in GISTs (P = 0.003).Conclusions:Overexpression of HSP90 is predictive of adverse behaviour in GISTs and may provide a therapeutic solution to the challenge of imatinib-resistant GISTs and other mesenchymal sarcomas.