Gastrointestinal stromal tumors: what do we know now?
Gastrointestinal stromal tumors: what do we know now?
复制标题
DOI：
10.1038/modpathol.2013.173
复制
发表时间：
2014-01-01
期刊：
影响因子：
7.5
通讯作者：
Corless, Christopher L.
中科院分区：
文献类型：
--
作者：
Corless, Christopher L.
胃肠道间质瘤（gist）是胃肠道最常见的间质肿瘤，起源于Cajal间质细胞，主要发生在胃和小肠。它们表现出广泛的形态，从梭形细胞到上皮样细胞，但基本上在所有病例中都对KIT （CD117）和/或DOG1免疫阳性。虽然大多数肿瘤在发病时是局部的，但有一半以上的肿瘤会在腹部复发或扩散到肝脏。大多数gist的生长是由两种受体酪氨酸激酶的致癌突变驱动的：KIT（75%的病例）或PDGFRA（10%）。用酪氨酸激酶抑制剂（TKIs）如伊马替尼、舒尼替尼和瑞非尼治疗可有效控制不可切除的疾病；然而，继发性KIT或PDGFRA突变导致的耐药最终在90%的病例中发生。伊马替尼辅助治疗通常用于降低原发性手术后疾病复发的可能性，因此评估新切除肿瘤的预后是病理学家最重要的角色之一。大约15%的gist在KIT和PDGFRA突变上呈阴性。最近对这些所谓的野生型gist的研究发现了许多其他的致癌驱动因素，包括I型神经纤维瘤病、RAS基因、BRAF和琥珀酸脱氢酶复合物亚基的突变。常规基因分型被强烈推荐用于gist的最佳管理，因为用于治疗的TKI的类型和剂量取决于所鉴定的突变。
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the GI tract, arising from the interstitial cells of Cajal, primarily in the stomach and small intestine. They manifest a wide range of morphologies, from spindle cell to epithelioid, but are immunopositive for KIT (CD117) and/or DOG1 in essentially all cases. Although most tumors are localized at presentation, up to half will recur in the abdomen or spread to the liver. The growth of most GISTs is driven by oncogenic mutations in either of two receptor tyrosine kinases: KIT (75% of cases) or PDGFRA (10%). Treatment with tyrosine kinase inhibitors (TKIs) such as imatinib, sunitinib, and regorafenib is effective in controlling unresectable disease; however, drug resistance caused by secondary KIT or PDGFRA mutations eventually develops in 90% of cases. Adjuvant therapy with imatinib is commonly used to reduce the likelihood of disease recurrence after primary surgery, and for this reason assessing the prognosis of newly resected tumors is one of the most important roles for pathologists. Approximately 15% of GISTs are negative for mutations in KIT and PDGFRA. Recent studies of these so-called wild-type GISTs have uncovered a number of other oncogenic drivers, including mutations in neurofibromatosis type I, RAS genes, BRAF, and subunits of the succinate dehydrogenase complex. Routine genotyping is strongly recommended for optimal management of GISTs, as the type and dose of TKI used for treatment is dependent on the mutation identified.