Agaram Narasimhan P, Baren Ann, Arkun Knarik, Dematteo Ronald P, Besmer Peter, Antonescu Cristina R
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Ultrastruct Pathol. 2006 Nov-Dec;30(6):443-52. doi: 10.1080/01913120600854186.
GISTs are the most common mesenchymal neoplasms of the digestive tract and are thought to originate from or differentiate toward the interstitial cell of Cajal lineage. Almost all GISTs express KIT protein and the majority show activating mutations in either KIT or PDGFRA proto-oncogenes. Ultrastructurally, these tumors have been shown to have either a smooth muscle, neuronal, dual, or null phenotype. The objective of this study was to investigate the relationship between ultrastructural features and genotype in a large series of 125 histologically confirmed and CD117 positive GISTs. PCR analysis for the presence of KIT exon 9, 11, 13, and 17 and PDGFRA exon 12 and 18 mutations was performed. There were 62 (50%) tumors located in the stomach and 45 (36%) in the small bowel. Overall, KIT mutations were detected in 93 (75%) patients: 86 (69%) in exon 11, and 7 (6%) in exon 9. A PDGFRA mutation was detected in 7 (6%) cases and 25 (19%) cases had no mutation. Ultrastructurally, skeinoid fibers were seen in 55 (44%) cases and were more common in small bowel than stomach GISTs, and occurred in only in 1 of 16 patients with an ITD (KIT) exon 11 or PDGFRA mutation. Focal actin microfilaments were identified in 82 (65%) cases and did not correlate with location or mutation type. Rare neurosecretory-type granules (NS-G) were seen in 34 (27%) of cases, but were seen in most of the cells in only 5 (4%) cases. GISTs showing both NS-G and microtubules were associated with KIT exon 11 genotype and spindle cell morphology. PDGFRA mutated cases were associated with gastric location, predominantly epithelioid morphology and lacked NS-G.
胃肠道间质瘤（GISTs）是消化道最常见的间叶性肿瘤，被认为起源于卡哈尔间质细胞系或向其分化。几乎所有的GISTs都表达KIT蛋白，并且大多数在KIT或血小板衍生生长因子受体α（PDGFRA）原癌基因中显示激活突变。在超微结构上，这些肿瘤已被证明具有平滑肌、神经元、双相或无表型。本研究的目的是在125例经组织学证实且CD117阳性的GISTs大样本中研究超微结构特征与基因型之间的关系。对KIT外显子9、11、13和17以及PDGFRA外显子12和18突变的存在进行了聚合酶链反应（PCR）分析。62例（50%）肿瘤位于胃，45例（36%）位于小肠。总体而言，在93例（75%）患者中检测到KIT突变：外显子11中有86例（69%），外显子9中有7例（6%）。在7例（6%）病例中检测到PDGFRA突变，25例（19%）病例无突变。在超微结构上，55例（44%）病例中可见绞丝状纤维，在小肠GISTs中比胃GISTs更常见，并仅出现在16例具有框内插入缺失（ITD，KIT）外显子11或PDGFRA突变的患者中的1例。82例（65%）病例中鉴定出局灶性肌动蛋白微丝，其与位置或突变类型无关。在34例（27%）病例中可见罕见的神经分泌型颗粒（NS-G），但仅在5例（4%）病例的大多数细胞中可见。同时显示NS-G和微管的GISTs与KIT外显子11基因型和梭形细胞形态相关。PDGFRA突变病例与胃的位置相关，主要为上皮样形态且缺乏NS-G。
