Zong Liang, Chen Ping
Department of Gastrointestinal Surgery, Su Bei People's Hospital of Jiangsu Province, Yangzhou University, Yangzhou, Jiangsu Province 225001, China.
World J Surg Oncol. 2014 Mar 28;12:71. doi: 10.1186/1477-7819-12-71.
The postulated relationship between KIT/PDGFRA mutations and their prognostic value in gastrointestinal stromal tumors (GISTs) has generated intense attention during the past decade, despite the fact that a great deal of studies have been conducted on this subject. To provide a strong quantitative estimate of this postulated relationship, we carried out a meta-analysis which combined, compared, and summarized the results of existing relevant studies.
Studies were identified by searching databases and reviewing citations in relevant articles. Of 48 potentially relevant studies, we combined individual patient data from 18 studies which involved 1,487 patients with GISTs, by which we made a comparison between the positive KIT mutation subgroup and the negative KIT mutation subgroup (PDGFRA mutation and wild type). We tabulated and analyzed the patient characteristics from each study, including general information such as age and gender, histopathological parameters, and clinical follow-up outcomes.
KIT mutations, compared with PDGFRA mutations and wild type, showed a marked increased risk not only for tumor size (>5 cm) but also for higher mitotic activity (>5), suggesting that KIT mutations significantly correlated with the National Comprehensive Cancer Network (NCCN) high risk or National Institutes of Health (NIH) high risk (1.74 (95% CI, 1.20 to 2.53) and 2.00 (95% CI, 1.08 to 3.68), respectively). Moreover, higher recurrence and metastasis was observed in GISTs with KIT mutations, revealing its closer correlation with clinical malignant risk (P<0.001 for each, with odds ratio (OR) of 2.06 (95%, 1.37 to 3.11) and 2.77 (95%, 1.64 to 4.67), respectively). High risk or malignant GISTs with KIT mutations had a significantly poorer prognosis, as measured by 3-year overall survival, compared to those with PDGFRA mutations and wild type (0.47 (95% CI, 0.25 to 0.90)).
KIT mutations, compared with PDGFRA mutations and wild type, represent a poorer prognostic marker in high risk or malignant GISTs.
尽管过去十年间针对该主题已开展了大量研究，但KIT/PDGFRA突变与胃肠道间质瘤（GIST）预后价值之间的假定关系仍备受关注。为了对这种假定关系进行有力的定量评估，我们进行了一项荟萃分析，综合、比较并总结了现有相关研究的结果。
通过检索数据库和查阅相关文章的参考文献来确定研究。在48项潜在相关研究中，我们合并了18项研究的个体患者数据，这些研究涉及1487例GIST患者，据此我们对KIT突变阳性亚组与KIT突变阴性亚组（PDGFRA突变和野生型）进行了比较。我们将每项研究的患者特征制成表格并进行分析，包括年龄和性别等一般信息、组织病理学参数以及临床随访结果。
与PDGFRA突变和野生型相比，KIT突变不仅显示出肿瘤大小（>5 cm）和有丝分裂活性较高（>5）的风险显著增加，这表明KIT突变与美国国立综合癌症网络（NCCN）高风险或美国国立卫生研究院（NIH）高风险显著相关（分别为1.74（95%可信区间，1.20至2.53）和2.00（95%可信区间，1.08至3.68））。此外，在有KIT突变的GIST中观察到更高的复发和转移率，这表明其与临床恶性风险的相关性更强（每项P<0.001，优势比（OR）分别为2.06（95%，1.37至3.11）和2.77（95%，1.64至4.67））。与有PDGFRA突变和野生型的GIST相比，有KIT突变的高风险或恶性GIST的3年总生存率预后明显更差（0.47（95%可信区间，0.25至0.90））。
与PDGFRA突变和野生型相比，KIT突变在高风险或恶性GIST中代表了较差的预后标志物。
