Effect of loss of heterozygosity of the c-kit gene on prognosis after hepatectomy for metastatic liver gastrointestinal stromal tumors
Effect of loss of heterozygosity of the c-kit gene on prognosis after hepatectomy for metastatic liver gastrointestinal stromal tumors
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DOI：
10.1111/j.1349-7006.2007.00592.x
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发表时间：
2007-11-01
期刊：
影响因子：
5.7
通讯作者：
Konno, Hiroyuki
中科院分区：
文献类型：
--
作者：
Kikuchi, Hirotoshi;Yamamoto, Masayoshi;Konno, Hiroyuki
作者此前曾报道，c-kit 基因杂合性缺失 (LOH) 可能是某些胃肠道间质瘤 (GIST) 获得高增殖活性的原因，从而导致转移潜力增强。在本研究中，试图确定可能预测转移性肝 GIST 患者术后预后的因素。研究人员检查了 14 名因异时性肝转移而接受肝切除术且未接受伊马替尼辅助治疗的患者的切除肝脏 GIST 的临床病理或遗传特征。 12例肝转移性GIST中有7例（58.3%）观察到c-kit基因的LOH，可提取出适合检测的DNA。十名患者在肝切除后出现复发，四名患者没有复发。肝切除术后的中位复发后无病生存期 (PRDFS) 为 27.5 个月（范围 8-104）。使用临床病理特征、c-kit 突变和 c-kit 基因的 LOH 检查肿瘤特异性 PRDFS。没有任何单一的临床病理学或遗传学发现与 PRDFS 显着相关。然而，“Ki67标记指数<5%且LOH(-)”的患者的PRDFS显着长于“Ki67>=5%或LOH(+)”的患者(P = 0.032)，并且c-kit基因LOH的存在与Ki67标记指数之间不存在相关性。转移性肝中c-kit基因的LOH似乎是一个常见事件，切除的肝GIST中c-kit基因的LOH可能是预测肝转移患者复发后预后的一个有用因素。
The authors have previously reported that loss of heterozygosity (LOH) of the c-kit gene could be responsible for the gain in high proliferative activity in some gastrointestinal stromal tumors (GIST), resulting in enhanced metastatic potential. In the present study, an attempt was made to identify the factors that might predict the postoperative prognosis of patients with metastatic liver GIST. The clinicopathologic or genetic features of resected liver GIST in 14 patients who had undergone a hepatectomy for metachronous liver metastases and who had not received adjuvant imatinib treatment were examined. LOH of the c-kit gene was observed in seven of 12 metastatic liver GIST (58.3%), of which DNA suitable for testing could be extracted. Ten patients had recurrence after hepatectomy and four had none. The median post-recurrent disease-free survival (PRDFS) after hepatectomy was 27.5 months (range 8-104). The tumor-specific PRDFS was examined using clinicopathologic features, c-kit mutation and LOH of the c-kit gene. No single clinicopathologic or genetic finding was significantly associated with PRDFS. However, patients with 'Ki67 labeling index < 5% and LOH(-)' had a significantly longer PRDFS than those with 'Ki67 >= 5% or LOH(+)' (P = 0.032), and there was no correlation between the presence of LOH of the c-kit gene and the Ki67 labeling index. LOH of the c-kit gene in metastatic liver seems to be a common event, and LOH of the c-kit gene in resected liver GIST may be a helpful factor in the prediction of the post-recurrent prognosis of patients with liver metastasis.