Immunohistochemical and genetic features of gastric and metastatic liver gastrointestinal stromal tumors: Sequential analyses
Immunohistochemical and genetic features of gastric and metastatic liver gastrointestinal stromal tumors: Sequential analyses
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DOI：
10.1111/j.1349-7006.2006.00154.x
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发表时间：
2006-02-01
期刊：
影响因子：
5.7
通讯作者：
Konno, H
中科院分区：
文献类型：
--
作者：
Kikuchi, H;Yamashita, K;Konno, H
转移性胃肠道间质瘤（GIST）预后极差；然而，其免疫组织化学和遗传特征尚未得到满意的评估，其高恶性潜能的机制仍不清楚。我们检查了4例因异时性肝转移而接受胃切除术后肝切除术的患者胃间质间质瘤和肝脏转移灶的免疫组织化学差异。我们还对其中3例的肿瘤进行了基因分析。在所有病例中，包括KIT （CD117）、CD34、平滑肌肌动蛋白（SMA）、clesmin、S-100和vimentin在内的免疫反应性特征在胃肿瘤和转移性肿瘤之间相似，但转移性GIST中的Ki67标记指数高于原发GIST。有趣的是，在胃切除术前接受新辅助伊马替尼治疗的病例中，除了特定的高细胞性小区域外，在大多数原发病变中观察到其治疗效果。遗传分析显示，在所有患者的转移性病变中，c-kit或PDGFRA基因均未发生获得性突变，但c-kit基因杂合性缺失（LOH）主要发生在3例患者中的2例转移性肿瘤中。此外，在新辅助伊马替尼治疗的情况下，c-kit基因的LOH出现在原发性病变和转移性肝GIST的高细胞区。提示c-kit基因LOH是导致GIST耐伊马替尼和转移进展的重要事件。综上所述，胃间质瘤和转移性间质瘤除了具有增殖活性外，其免疫组化特征几乎相同，c-kit基因LOH在肝转移过程中发挥了重要作用。
Metastatic gastrointestinal stromal tumors (GIST) have an extremely poor prognosis; however, their immunohistochemical and genetic features have not been assessed satisfactorily and the mechanisms responsible for their high malignant potential remain unclear. We examined the immunohistochemical differences between gastric GIST and metastatic lesions in the liver of four patients who had undergone a postgastrectomy hepatectomy for metachronous liver metastases. We also carried out genetic analysis of the tumors in three of the four cases. In all cases, the immunoreactivity profiles, including KIT (CD117), CD34, smooth muscle actin (SMA), clesmin, S-100 and vimentin, were similar between the gastric and metastatic tumors, but the Ki67 labeling index in the metastatic GIST was higher than that of the primary GIST. Interestingly, in the case who had received neoadjuvant imatinib therapy before gastrectomy, its therapeutic effect was observed in most of the primary lesion, with the exception of a specific small area with high cellularity. Genetic analysis revealed no acquired mutations in the c-kit or PDGFRA genes in the metastatic lesions in any of the patients, but loss of heterozygosity (LOH) of the c-kit gene was observed mainly in the metastatic tumors in two of the three cases. Furthermore, in the case of neoadjuvant imatinib therapy, LOH of the c-kit gene was shown in the high cellularity area in the primary lesion and metastatic liver GIST. It is suggested that LOH of the c-kit gene is an important event that leads to imatinib resistance and metastatic progression of GIST. In conclusion, both gastric and metastatic GIST had almost the same immunohistochemical features, except for their proliferative activity, and LOH of the c-kit gene played an important role in the process of liver metastasis.