Department of Gastrointestinal Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China.
World J Gastroenterol. 2018 Jun 21;24(23):2508-2517. doi: 10.3748/wjg.v24.i23.2508.
To detect the expression of Raf kinase inhibitory protein (RKIP) in gastrointestinal stromal tumors (GISTs) and to analyze its relationship with clinicopatholgical characteristics and prognosis of this disease.
Sixty-three patients with pathologically diagnosed GISTs who underwent surgical resection at the Shengjing Hospital of China Medical University from January 2011 to January 2015 and had complete clinical, pathological, and follow-up data were included. Immunohistochemical method was used to detect the expression of RKIP in GIST tissue samples from these patients. Kaplan-Meier method was used to calculate the survival rate of 60 patients with complete follow-up data, and Cox regression analysis was performed to identify factors affecting the prognosis of patients GISTs to evaluate further the diagnostic and prognostic value of RKIP in GISTs.
In GIST tissues, RKIP positive signals, manifesting as brownish yellow or brown granules, were located in the cytoplasm or on the membrane. Of 63 tissue samples included in this study, 34 (54%) were positive and 29 (46%) were negative for RKIP expression. Statistical analysis showed that RKIP expression in GISTs was significantly associated with tumor size, National Institutes of Health (NIH) risk grade, and mucosal invasion, but had no significant association with age, gender, tumor location, or the number of mitotic figures. Univariate Kaplan-Meier analysis revealed that the 1-, 3-, and 5-year survival rates were 94.4%, 89.2%, and 80.5% for patients with positive RKIP expression, and 88.6%, 68.2%, and 48.2% for patients with negative RKIP expression, suggesting that patients with high RKIP expression had significantly higher survival rates than those with low expression (Log-rank test, = 0.0015). Cox regression analysis demonstrated that NIH risk grade was significantly associated with the prognosis of GISTs ( = 0.037), suggesting that NIH risk grade is a significant predictor of the prognosis of GISTs. RKIP expression had a tendency to predict the survival of GISTs ( = 0.122), suggesting that RKIP expression may have appreciated value to predict the prognosis of GISTs.
This study demonstrated that: (1) RKIP expression in GISTs is associated with tumor size, NIH risk grade, and mucosal invasion, and low or no expression of RKIP predicts a high malignancy potential; (2) high RKIP correlates positively with the survival of patients with GISTs; and (3) RKIP expression has appreciated value for predicting the survival of patients with GISTs, although it is not an independent prognostic factor in GISTs.
检测雷帕霉素靶蛋白激酶抑制蛋白（RKIP）在胃肠道间质瘤（GISTs）中的表达情况，并分析其与该疾病临床病理特征和预后的关系。
纳入 2011 年 1 月至 2015 年 1 月在中国医科大学盛京医院接受手术切除且具有完整临床、病理和随访资料的 63 例经病理诊断为 GIST 的患者。采用免疫组织化学方法检测这些患者 GIST 组织样本中 RKIP 的表达情况。采用 Kaplan-Meier 法计算 60 例具有完整随访资料患者的生存率，并进行 Cox 回归分析以确定影响 GIST 患者预后的因素，进一步评估 RKIP 在 GIST 中的诊断和预后价值。
在 GIST 组织中，RKIP 阳性信号表现为棕黄色或棕色颗粒，位于细胞质或细胞膜上。在本研究纳入的 63 个组织样本中，34 个（54%）为阳性，29 个（46%）为阴性。统计学分析显示，GIST 中 RKIP 的表达与肿瘤大小、美国国立卫生研究院（NIH）危险度分级和黏膜浸润显著相关，而与年龄、性别、肿瘤部位或有丝分裂计数无显著关系。单因素 Kaplan-Meier 分析显示，RKIP 表达阳性患者的 1、3 和 5 年生存率分别为 94.4%、89.2%和 80.5%，而 RKIP 表达阴性患者的生存率分别为 88.6%、68.2%和 48.2%，提示 RKIP 高表达患者的生存率明显高于低表达患者（Log-rank 检验， = 0.0015）。Cox 回归分析显示，NIH 危险度分级与 GIST 预后显著相关（ = 0.037），提示 NIH 危险度分级是 GIST 预后的一个显著预测因子。RKIP 表达有预测 GIST 患者生存的趋势（ = 0.122），提示 RKIP 表达可能对预测 GIST 患者的预后具有一定价值。
本研究表明：（1）GIST 中 RKIP 的表达与肿瘤大小、NIH 危险度分级和黏膜浸润有关，低表达或无表达预示着高恶性潜能；（2）高 RKIP 与 GIST 患者的生存呈正相关；（3）虽然 RKIP 表达不是 GIST 的独立预后因素，但对预测 GIST 患者的生存具有一定价值。
