Loss of RKIP expression is associated with poor survival in GISTs
Loss of RKIP expression is associated with poor survival in GISTs
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DOI：
10.1007/s00428-009-0821-z
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发表时间：
2009-09-01
期刊：
影响因子：
3.5
通讯作者：
Lopes, Jose Manuel
中科院分区：
文献类型：
--
作者：
Martinho, Olga;Gouveia, Antonio;Lopes, Jose Manuel
胃肠道间质瘤（GIST）是一种罕见的消化道间质肿瘤，通常由KIT和PDGFRA基因的致癌突变驱动。肿瘤大小、位置、有丝分裂指数和KIT/PDGFRA突变是GIST最重要的预后参数。然而，在GIST中筛选新的分子预后标志物的其他研究缺失。Raf激酶抑制蛋白（RKIP）已被认为是一个抑制转移和预后标志物在一些肿瘤。在本研究中，我们的目的是检查是否RKIP表达与GIST的临床病理特征。使用免疫组化，我们确定了RKIP的表达水平在一个良好的表征系列的70 GIST。我们发现RKIP在绝大多数病例中表达，在约9%的GIST中不表达。此外，我们发现RKIP表达的丧失不是由于甲基化特异性PCR评估的启动子甲基化。RKIP表达缺失与GIST的疾病特异性生存率低和肿瘤坏死相关。RKIP阳性表达与无转移之间存在统计学趋势。到目前为止，这是第一项评估GIST中RKIP表达水平的研究。我们的结论是，RKIP表达的损失可能有一个重要的作用，作为GIST的预后指标。
Gastrointestinal stromal tumours (GISTs) are rare mesenchymal tumours of the digestive tract and are commonly driven by oncogenic mutations in KIT and PDGFRA genes. Tumour size, location, mitotic index and KIT/PDGFRA mutations are the most important prognostic parameters in GISTs. However, additional studies screening for new molecular prognostic markers in GISTs are missing. Raf kinase inhibitor protein (RKIP) has been considered as a suppressor of metastasis and a prognostic marker in several neoplasms. In the present study we aimed to examine whether RKIP expression is associated with GIST clinical-pathological features. Using immunohistochemistry, we determined RKIP expression levels in a well-characterised series of 70 GISTs. We found that RKIP is expressed in the great majority of cases, and absent in approximately 9% of GISTs. Additionally, we found that loss of RKIP expression was not due to the promoter methylation as assessed by methylation-specific PCR. Loss of RKIP expression was associated with poor disease-specific survival and with tumour necrosis in GISTs. Furthermore, a statistical tendency was observed between the positive RKIP expression and absence of metastasis. So far, this is the first study assessing RKIP expression levels in GISTs. We conclude that loss of RKIP expression could have an important role as prognostic marker in GISTs.