Multiple gastrointestinal stromal tumors in type I neurofibromatosis: a pathologic and molecular study
Multiple gastrointestinal stromal tumors in type I neurofibromatosis: a pathologic and molecular study
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DOI：
10.1038/modpathol.3800334
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发表时间：
2005-04-01
期刊：
影响因子：
7.5
通讯作者：
Antonescu, CR
中科院分区：
文献类型：
--
作者：
Yantiss, RK;Rosenberg, AE;Antonescu, CR
多发性胃肠道间质瘤通常以家族形式发生，与KIT受体酪氨酸激酶或血小板源性生长因子受体-α（PDGFRA）种系突变相关，但也可能在1型神经纤维瘤病的背景下发生。神经纤维瘤病引起的胃肠道间质瘤的分子异常尚未得到广泛的研究。我们确定了三名1型神经病患者。纤维瘤病和多发性小肠间质瘤。对所有肿瘤进行CD 117、CD 34、结蛋白、肌动蛋白、S-100蛋白和角蛋白的免疫染色。在每种情况下，从来自单独肿瘤结节的代表性石蜡块中提取DNA，并使用针对KIT外显子9、11、13和17以及PDGFRA外显子12和18的引物进行巢式聚合酶链反应，然后进行直接测序。患者平均年龄为56岁（范围：37-86岁，男性/女性比例：2/1）。1例患者有3个肿瘤，1例有5个肿瘤，1例有10个以上的肿瘤结节，所有这些肿瘤均表现出胃肠道间质瘤的组织学特征，CD 117和CD 34染色强烈。1例患者在35个月时死于疾病，1例在12个月时无疾病，1例失访。对10例胃肠道间质瘤（2例患者各3例，1例患者4例）的DNA提取物进行聚合酶链反应并评估突变。所有肿瘤对于KIT外显子9、13和17以及PDGFRA外显子12和18而言均为野生型。来自一名患者的三个肿瘤在KIT外显子11中具有相同的点突变，而其他肿瘤在该位点为野生型。我们的结论是，虽然大多数1型神经纤维瘤病和胃肠道间质瘤患者没有KIT或PDGFRA突变，KIT生殖细胞突变可能与胃肠道间质瘤的发病机制在一些患者。
Multiple gastrointestinal stromal tumors typically occur in familial form associated with KIT receptor tyrosine kinase or platelet-derived growth factor receptor-alpha (PDGFRA) germline mutations, but may also develop in the setting of type 1 neurofibromatosis. The molecular abnormalities of gastrointestinal stromal tumors arising in neurofibromatosis have not been extensively studied. We identified three patients with type 1 neuro. fibromatosis and multiple small intestinal stromal tumors. Immunostains for CD117, CD34, desmin, actins, S-100 protein, and keratins were performed on all of the tumors. DNA was extracted from representative paraffin blocks from separate tumor nodules in each case and subjected to a nested polymerase chain reaction, using primers for KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18, followed by direct sequencing. The mean patient age was 56 years (range: 37-86 years, male/female ratio: 2/1). One patient had three tumors, one had five, and one had greater than 10 tumor nodules, all of which demonstrated histologic features characteristic of gastrointestinal stromal tumors and stained strongly for CD117 and CD34. One patient died of disease at 35 months, one was disease free at 12 months and one was lost to follow-up. DNA extracts from 10 gastrointestinal stromal tumors (three from each of two patients and four from one patient) were subjected to polymerase chain reactions and assessed for mutations. All of the tumors were wild type for KIT exons 9, 13, and 17 and PDGFRA exons 12 and 18. Three tumors from one patient had identical point mutations in KIT exon 11, whereas the other tumors were wild type at this locus. We conclude that, although most patients with type 1 neurofibromatosis and gastrointestinal stromal tumors do not have KIT or PDGFRA mutations, KIT germline mutations might be implicated in the pathogenesis of gastrointestinal stromal tumors in some patients.