Succinate dehydrogenase-deficient GISTs are characterized by IGF1R overexpression
Succinate dehydrogenase-deficient GISTs are characterized by IGF1R overexpression
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DOI：
10.1038/modpathol.2012.77
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发表时间：
2012-09-01
期刊：
影响因子：
7.5
通讯作者：
Gill, Anthony J.
中科院分区：
文献类型：
--
作者：
Chou, Angela;Chen, Jason;Gill, Anthony J.
琥珀酸脱氢酶缺陷型胃肠道间质瘤（GIST）表现出独特的病理和临床特征，包括缺乏KIT和PDGFRA的激活突变，以及对伊马替尼的原发性耐药。它们仅发生在胃中，占所有成人胃GIST的5-7.5%，并且绝大多数这些肿瘤发生在儿童时期。胰岛素样生长因子1受体（IGF 1 R）过表达与野生型和儿科GIST相关。我们认为IGF 1 R过表达是琥珀酸脱氢酶缺陷型GIST的一个特征。我们通过免疫组化评估了8例已知琥珀酸脱氢酶缺陷型GIST、3例1型神经纤维瘤综合征引起的GIST和40例GIST中琥珀酸脱氢酶复合物亚基B（SDHB）和IGF 1 R的表达。从福尔马林固定石蜡包埋的肿瘤样本中扩增选定的KIT和PDGFRA外显子并测序。所有8例琥珀酸脱氢酶缺陷型肿瘤均为KIT和PDGFRA野生型，琥珀酸脱氢酶B阴性，并显示IGF 1 R过表达。3例神经纤维瘤病相关肿瘤均为琥珀酸脱氢酶B阳性，IGF 1 R阴性。在40个以上的GIST中，5个在所选外显子中为KIT和PDGFRA野生型。2例野生型GIST为琥珀酸脱氢酶B阴性，显示IGF 1 R过表达，3例为琥珀酸脱氢酶B阳性，IGF 1 R阴性。我们的结论是IGF 1 R的过度表达是琥珀酸脱氢酶缺陷型GIST的一个特征，而不是儿童或野生型GIST本身。因此，IGF 1 R抑制剂是一种潜在的合理的治疗方法，在这个最近公认的亚组GIST。Modern Pathology（2012）25，1307-1313; doi：10.1038/modpathol.2012.77; 2012年5月4日在线发表
Succinate dehydrogenase-deficient gastrointestinal stromal tumors (GISTs) demonstrate unique pathological and clinical features, including the absence of activating mutations of KIT and PDGFRA, and primary resistance to imatinib. They arise exclusively in the stomach and account for 5-7.5% of all adult stomach GISTs and the great majority of these tumors in childhood. Insulin-like growth factor 1 receptor (IGF1R) overexpression has been associated with wild-type and pediatric GISTs. We propose that IGF1R overexpression is a feature of succinate dehydrogenase-deficient GISTs as a group. We assessed succinate dehydrogenase complex subunit B (SDHB) and IGF1R expression by immunohistochemistry in eight known succinate dehydrogenase-deficient GISTs, three GISTs arising in the setting of neurofibromatosis type 1 syndrome and 40 unselected GISTs. Selected KIT and PDGFRA exons were amplified and sequenced from formalin-fixed paraffin-embedded tumor samples. All eight succinate dehydrogenase-deficient tumors were wild-type for KIT and PDGFRA, succinate dehydrogenase B negative and demonstrated IGF1R overexpression. The three neurofibromatosis-related tumors were succinate dehydrogenase B positive and IGF1R negative. Of the 40 unselected upper GISTs, five were wild-type for KIT and PDGFRA in the selected exons. Two of the wild-type GISTs were succinate dehydrogenase B negative and showed IGF1R overexpression and three were succinate dehydrogenase B positive and IGF1R negative. We conclude that IGF1R overexpression is a feature of succinate dehydrogenase deficient GIST as a group, rather than pediatric or wild-type GIST per se. Therefore, IGF1R inhibition represents a potential rational therapeutic approach in this recently recognized subgroup of GIST. Modern Pathology (2012) 25, 1307-1313; doi:10.1038/modpathol.2012.77; published online 4 May 2012