Gastrointestinal stromal tumors (GIST): C-kit mutations, CD117 expression, differential diagnosis and targeted cancer therapy with imatinib
Gastrointestinal stromal tumors (GIST): C-kit mutations, CD117 expression, differential diagnosis and targeted cancer therapy with imatinib
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DOI：
10.1007/bf03033708
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发表时间：
2003-01-01
影响因子：
2.8
通讯作者：
Reid, R
中科院分区：
文献类型：
--
作者：
de Silva, MV;Reid, R
胃肠道间质瘤（GIST）已被认为是一种生物学上独特的肿瘤类型，不同于胃肠道平滑肌和神经肿瘤。它们构成了大多数胃肠道间叶肿瘤。通过免疫组织化学检测一种称为CD 117的原癌基因蛋白的表达来定义和诊断它们。现在认为GIST起源于称为Cajal间质细胞的胃肠起搏细胞，其控制肠道运动或这些细胞的前体。在许多GIST中，c-kit原癌基因编码c-kit（CD 117）的外显子11和外显子9和13中的突变主要发生在外显子11中，较小程度上发生在外显子9和13中，这使得对其致癌机制有了更好的理解。分子抑制剂伊马替尼（Glivec（TM））在转移性和不可手术的GIST中的显着抗肿瘤作用的发现使得GIST的准确诊断及其与其他胃肠道间叶肿瘤的区别成为必要。为了实现这一目标，病理学家需要熟悉GIST所显示的组织学表现谱，并对这些肿瘤具有高度怀疑。本文综述了GIST的组织发生、病理学、分子生物学、遗传学和鉴别诊断方面的最新进展，以及伊马替尼用于新型靶向癌症治疗的基础。
Gastrointestinal stromal tumors (GISTs) have been recognised as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract. They constitute the majority of gastrointestinal mesenchymal tumors. They are defined and diagnosed by the expression of a protooncogene protein called CD117 detected by immunohistochemistry. It is now believed that GISTs originate from gastrointestinal pacemaker cells known as interstitial cells of Cajal, that control gut motility or from a precursor of these cells. The identification of mutations mostly in exon 11 and to a lesser extent in exons 9 and 13 of the c-kit protooncogene coding for c-kit (CD117) in many GISTs, has resulted in a better understanding of their onco-genic mechanisms. The finding of remarkable antitumor effects of the molecular inhibitor, imatinib (Glivec(TM)) in metastatic and inoperable GISTs, has necessitated accurate diagnosis of GISTs and their distinction from other gastrointestinal mesenchymal tumors. To achieve this, pathologists need to be familiar with the spectrum of histological appearances shown by GISTs and have a high index of suspicion for these tumors. This review summarises recent advances in knowledge regarding the histogenesis, pathology, molecular biology, genetics and differential diagnosis of GISTs and the basis for the novel targeted cancer therapy with imatinib.