de Silva Chandu M V, Reid Robin
University Department of Pathology, Western Infirmary, Glasgow, G11 6NT, UK.
Pathol Oncol Res. 2003;9(1):13-9. doi: 10.1007/BF03033708. Epub 2003 Apr 18.
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 oncogenic mechanisms. The finding of remarkable antitumor effects of the molecular inhibitor, imatinib (Glivec trade mark ) 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.
胃肠道间质瘤（GISTs）已被公认为一种生物学特性独特的肿瘤类型，不同于胃肠道的平滑肌肿瘤和神经肿瘤。它们构成了胃肠道间叶性肿瘤的大部分。通过免疫组织化学检测到的一种称为CD117的原癌基因蛋白的表达来定义和诊断它们。现在认为，GISTs起源于控制肠道蠕动的胃肠道起搏细胞，即 Cajal 间质细胞，或起源于这些细胞的前体。在许多GISTs中，大多在编码c-kit（CD117）的c-kit原癌基因的第11外显子中发现突变，在第9和13外显子中发现的突变较少，这使得人们对其致癌机制有了更好的理解。分子抑制剂伊马替尼（商品名格列卫）对转移性和不可切除的GISTs具有显著的抗肿瘤作用，这就需要对GISTs进行准确诊断，并将其与其他胃肠道间叶性肿瘤区分开来。为了实现这一点，病理学家需要熟悉GISTs所表现出的组织学表现谱，并对这些肿瘤有高度的怀疑指数。本综述总结了关于GISTs的组织发生学､病理学､分子生物学､遗传学和鉴别诊断的最新知识进展，以及伊马替尼新型靶向癌症治疗的基础。
