胃肠间质瘤中Ki-67表达对患者预后的作用

Influence of Ki-67 expression on the prognosis of gastrointestinal stromal tumors

目的分析胃肠间质瘤(gastrointestinal stromal tumors,GIST)患者Ki-67指数的表达情况,探讨其与GIST患者疾病进展的关系。方法139例GIST患者,均在腹腔镜下行间质瘤切除术,采用免疫组织化学法检测手术切除组织中Ki-67指数;记录患者临床资料并进行随访,根据疾病有无进展(或死亡)分为进展组33例和无进展组106例,比较2组年龄、性别、肿瘤原发位置、肿瘤直径、肿瘤细胞核分裂象计数和肿瘤组织Ki-67指数;采用多因素Cox比例风险回归模型分析GIST患者疾病进展的影响因素;绘制ROC曲线,评估Ki-67指数对GIST患者疾病进展的预测效能;采用Kaplan-Meier生存曲线分析不同Ki-67指数的GIST患者5年无进展生存率的差异。结果进展组Ki-67指数[15.0(10.0,22.5)%]大于无进展组[5.0(3.0,8.0)%](P<0.05),肿瘤直径[11.0(7.8,13.0)cm]、核分裂象计数[13.5(1.8,17.3)个/50HPF]、非胃原发肿瘤比率(51.5%)及中、高危患者比率(96.9%)均高于无进展组[5.5(3.0,8.0)cm、6.0(4.0,9.0)/50HPF、37.7%、69.8%](P<0.05);原发肿瘤部位(HR=1.501,95%CI:1.049~2.148,P=0.026)、肿瘤直径(HR=1.762,95%CI:1.067~2.909,P=0.027)、核分裂象计数(HR=1.667,95%CI:1.026~2.709,P=0.039)、Ki-67指数(HR=2.635,95%CI:1.033~6.720,P=0.043)是GIST患者疾病进展的影响因素。Ki-67指数最佳截断值为8%,预测GIST患者疾病进展的AUC为0.846(95%CI:0.772~0.921,P<0.001)。Ki-67指数>8%患者无进展生存率(60.9%)低于Ki-67指数≤8%者(91.4%)(P<0.05)。结论原发肿瘤部位、肿瘤直径、核分裂象计数、Ki-67指数是GIST患者疾病进展的影响因素,GIST患者Ki-67指数升高提示疾病进展。

Objective To analyze the expression of Ki-67 in patients with gastrointestinal stromal tumors(GIST),and to explore its relationship with the progression of GIST.Methods Totally 139 patients with GIST underwent laparoscopic GIST resection.Immunohistochemical method was used to detect Ki-67 index in the resected tissues.The clinical data were recorded and the follow-up was done.According to the progression,139 patients were divided into progression group(n=33)and non-progression group(n=106).The age,gender,tumor primary position,tumor diameter,mitosis count and Ki-67 index were compared between two groups.Multivariate Cox proportional hazards regression model was used to analyze the influencing factors of progression in GIST patients.ROC curve was drawn to evaluate the predictive efficiency of Ki-67 on the progression in patients with GIST.Kaplan-Meier survival curve was used to analyze the difference of 5-year survival rates in patients with different Ki-67 indexes.Results The Ki-67 index was larger in progression group(15.0(10.0,22.5)%)than that in non-progression group(5.0(3.0,8.0)%)(P<0.05).The tumor diameter was longer,and the mitosis count,the percentage of non-primary stomach tumors,and the percentage of mederate-to high-risk patients were higher in progression group(11.0(7.8,13.0)cm,13.5(1.8,17.3)/50 HPF,51.5%,96.9%)than those in non-progression group(5.5(3.0,8.0)cm,6.0(4.0,9.0)/50 HPF,37.7%,69.8%)(P<0.05).The tumor primary position(HR=1.501,95%CI:1.049-2.148,P=0.026),tumor diameter(HR=1.762,95%CI:1.067-2.909,P=0.027),mitosis count(HR=1.667,95%CI:1.026-2.709,P=0.039),and Ki-67 index(HR=2.635,95%CI:1.033-6.720,P=0.043)were the influencing factors of progression.When the optimal cut-off value of Ki-67 index was 8%,the AUC for predicting progression was 0.846(95%CI:0.772-0.921,P<0.001).The progression-free survival rate was lower in patients with Ki-67 index of>8%(60.9%)than that in patients with Ki-67 index of≤8%(91.4%)(P<0.05).Conclusion The tumor primary position,tumor diameter,mitosis count and Ki-67 index are the influencing factors of GIST progression.The increased Ki-67 index indicates the progression in GIST patients.