Expression of the Receptor for Type I Insulin-like Growth Factor (IGF1R) in Gastrointestinal Stromal Tumors An Immunohistochemical Study of 1078 Cases With Diagnostic and Therapeutic Implications
Expression of the Receptor for Type I Insulin-like Growth Factor (IGF1R) in Gastrointestinal Stromal Tumors An Immunohistochemical Study of 1078 Cases With Diagnostic and Therapeutic Implications
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DOI：
10.1097/pas.0b013e3182613c86
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发表时间：
2013-01-01
影响因子：
5.6
通讯作者：
Miettinen, Markku
中科院分区：
文献类型：
--
作者：
Lasota, Jerzy;Wang, Zengfeng;Miettinen, Markku
大多数胃肠道间质瘤 (GIST) 携带功能获得性 KIT 或血小板衍生生长因子受体 a (PDGFRA) 突变。然而，在儿科胃 GIST、神经纤维瘤病 1 相关 GIST 和一小部分成人散发性 GIST [所谓的野生型 (WT) GIST] 中，尚未发现 KIT 或 PDGFRA 的突变激活。最近，发现儿童胃 GIST 和一些成人 WT 胃 GIST 存在琥珀酸脱氢酶 (SDH) 复合物（一种克雷布斯循环/电子传递链界面蛋白）的丢失，如 SDH 亚基 B (SDHB) 表达的免疫组织化学丢失所示。此外，最近，尽管只分析了少量病例，但在儿科和 WT GIST 中检测到了 I 型胰岛素样生长因子 (IGF1R) 受体的表达。在这项研究中，通过免疫组织化学方法检查了 1078 个代表不同临床遗传学类别的明确表征的 GIST 和 103 个非 GIST 胃肠道肿瘤中的 IGF1R 表达。在 71/80 的 SDH 缺陷 GIST（SDHB 阴性 GIST）中检测到 IGF1R 表达，但仅在 9/625（1%）的 SDHB 阳性胃 GIST 中检测到。后者通常携带 KIT 或 PDGFRA 突变，并且通常发生在老年患者中。 373 个肠道 GIST 均未呈 IGF1R 阳性，而许多原发性肠道肉瘤，包括透明细胞肉瘤、平滑肌肉瘤和未分化肉瘤，均为 IGF1R 阳性。肠道 GIST 中始终缺乏 IGF1R 表达应被视为鉴别诊断 GIST 和非 GIST 肉瘤的额外免疫组织化学标志物。由于 IGF1R 信号传导的抑制可能成为 GIST 的治疗靶点，因此筛选 IGF1R 表达在不久的将来可能会变得重要。
A majority of gastrointestinal stromal tumors (GISTs) carry gain-of-function KIT or platelet-derived growth factor receptor a (PDGFRA) mutations. However, no mutational activation of KIT or PDGFRA has been identified in pediatric gastric GISTs, neurofibromatosis-1-associated GISTs, and a small subset of sporadic GISTs in adults [so-called wild-type (WT) GISTs]. Recently, pediatric gastric GISTs and some adult WT gastric GISTs have been found to have losses of the succinate dehydrogenase (SDH) complex, a Krebs cycle/electron transport chain interface protein, as seen by immunohistochemical loss of SDH subunit B (SDHB) expression. Moreover, recently, expression of the receptor for type I insulin-like growth factor (IGF1R) has been detected in pediatric and WT GISTs, although only a small number of cases have been analyzed. In this study, IGF1R expression was examined immunohistochemically in 1078 well-characterized GISTs representing different clinicogenetic categories and in 103 non-GIST gastrointestinal tumors. IGF1R expression was detected in 71/80 of SDH-deficient GISTs (SDHB-negative GISTs) but only in 9/625 (1%) of the SDHB-positive gastric GISTs. The latter often carried KIT or PDGFRA mutations and generally occurred in older patients. None of the 373 intestinal GISTs was IGF1R positive, whereas many primary intestinal sarcomas, including clear cell sarcomas, leiomyosarcomas, and undifferentiated sarcomas, were IGF1R positive. The consistent lack of IGF1R expression in intestinal GISTs should be considered an additional immunohistochemical marker in the differential diagnosis between GISTs and non-GIST sarcomas. Because inhibition of IGF1R signaling might become a therapeutic target in GISTs, screening for IGF1R expression may become important in the near future.