Fine-needle aspiration biopsy diagnosis of gastrointestinal stromal tumors using morphology, immunocytochemistry, and mutational analysis of c-kit
Fine-needle aspiration biopsy diagnosis of gastrointestinal stromal tumors using morphology, immunocytochemistry, and mutational analysis of c-kit
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DOI：
10.1002/cncr.9041
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发表时间：
2001-08-25
影响因子：
3.4
通讯作者：
Heinrich, MC
中科院分区：
文献类型：
--
作者：
Rader, AE;Avery, A;Heinrich, MC
背景资料。细针吸取活检(FNAB)很难将胃肠道间质瘤(GIST)与胃肠道其他壁间充质瘤区分开来。最近的研究表明，GIST具有免疫表型和遗传差异。科学家表现出一致的CD-117(KIT)的免疫组织化学表达，并经常表达这种原癌基因的激活突变。方法回顾1998~1999年在俄勒冈州波特兰市退伍军人事务医学中心(VAMC)进行的5例胃肠道梭形细胞肿瘤的免疫细胞化学和c-kit基因突变分析。对每个细胞块进行一系列免疫细胞化学染色，包括CD-117(试剂盒)、平滑肌肌动蛋白(SMA)、结蛋白、S-100和CD34。提取基因组DNA(GDNA)，对CD-117(KIT)和CD34阳性病例进行c-kit外显子9、11、13和17的聚合酶链式反应(PCR)扩增。扩增产物直接测序鉴定突变。结果：5名患者根据细胞形态和CD-117和CD34免疫细胞化学阳性诊断为胃肠道间质瘤。C-kit外显子11的聚合酶链式反应分析显示，除了预期的野生型聚合酶链式反应产物外，还有三例患者的聚合酶链式反应条带大小新颖。这些病例的扩增产物含有框内缺失突变。两例野生型外显子11扩增片段中的一例被发现为产生氨基酸替代的点突变杂合子(W557R)。结论免疫细胞化学和c-kit基因突变分析等辅助技术有助于诊断FNAB的GIST。(C)2001年美国癌症协会。
BACKGROUND. Differentiating gastrointestinal stromal tumors (GISTs) from other intramural mesenchymal tumors of the GI tract on fine-needle aspiration biopsies (FNABs) is difficult. Recent studies have shown that GISTs are immunophenotypically and genetically distinct. GISTs exhibit consistent immunohistochemical ex pression of CD-117 (KIT) and often express activating mutations of this protooncogene. The aim of the current study was to employ immunocytochemistry and mutational analysis of the c-kit gene to aid in the diagnosis of GISTs on FNAB.METHODS. Five endoscopic ultrasound-guided FNABs of gastrointestinal spindle cell neoplasms performed at the Veterans Affairs Medical Center (VAMC) in Portland, Oregon, from 1998-1999 were reviewed. A panel of immunocytochemical stains was performed on each cellblock including CD-117 (KIT), smooth muscle actin (SMA), desmin, S-100, and CD34. Genomic DNA (gDNA) was extracted, and amplification of exons 9, 11, 13 and 17 of c-kit was performed by polymerase chain reaction (PCR) on CD-117 (KIT) and CD34 positive cases. Direct sequencing of amplicons identified the mutations.RESULTS. Five patients were diagnosed with GISTs based on morphology and immuno cyto chemical positivity for CD-117 and CD34. PCR analysis of c-kit exon 11 revealed three cases with novel-sized PCR bands in addition to the expected wild-type-sized PCR product. Amplicons from these cases contained an in-frame deletion mutation. One of the two cases with wild-type-;sized exon 11 amplicons was found to be heterozygous for a point mutation producing an amino acid substitution (W557R). No mutations in exon 9, 11, 13, or 17 of c-kit were found in the remaining case.CONCLUSIONS. Ancillary techniques such as immuno cyto chemistry and c-kit gene mutational analysis may aid in the diagnosis of GISTs on FNABs. (C) 2001 American Cancer Society.