超声造影联合免疫组织化学诊断小肝细胞癌微血管侵犯:两个医院的回顾性研究

Contrast enhanced ultrasound combined with immunohistochemistry in the diagnosis of microvascular invasion of small hepatocellular carcinoma:a retrospective study in two hospitals

目的探讨超声造影(contrast enhanced ultrasound,CEUS)联合免疫组织化学(immunohistochemistry,IHC)在术前诊断小肝细胞癌(hepatocellular carcinoma,HCC)微血管侵犯(microvascular invasion,MVI)中的价值。方法回顾性收集日本横滨市立大学附属市民综合医疗中心和西安交通大学第一附属医院142例HCC患者的资料,包括177个新发的、最大直径不超过3 cm的HCC病灶。根据手术切除标本的病理学诊断分为MVI(+)组(n=37)和MVI(-)组(n=140)。在术前CEUS动脉期(arterial phase,AP)和血管后期(post‐vascular phase,PVP)图像上分别观察病灶周边有无高灌注、低灌注;采用IHC检测热休克蛋白70(heat shock protein,HSP70)、磷脂酰肌醇蛋白聚糖3(glypican 3,GPC3)在术前穿刺活检标本中的表达。结果CEUS指标(AP、PVP)和IHC指标(GPC3、HSP70)单独诊断MVI时,PVP的诊断效率最高,准确率为91.0%,ROC曲线下面积(area under curve,AUC)为0.893。GPC3+HSP70联合诊断的效能(准确率为79.8%,AUC为0.790)优于单独GPC3(准确率为69.5%,AUC为0.752)或单独HSP70(准确率为60.7%,AUC为0.701)诊断,其中PVP+GPC3+HSP70联合诊断的效能最优,特异度为98.5%,准确率为92.5%,AUC为0.840。结论观察CEUS的PVP并使用IHC检测GPC3、HSP70的表达情况可在术前较好地诊断小HCC的MVI。

Objective To investigate the value of the contrast enhanced ultrasound(CEUS)combined with immunohistochemistry(IHC)in preoperative diagnosis of microvascular invasion(MVI)of small hepatocellular carcinoma(HCC).Methods The data of 142 HCC patients,including 177 newly developed HCC lesions with a maximum diameter of no more than 3 cm were retrospectively collected from the Yokohama City University Medical Center of Japan and the First Affiliated Hospital of Xi'an Jiaotong University.According to the pathological diagnosis,the patients were divided into MVI(+)group(n=37)and MVI(-)group(n=140).Preoperative CEUS arterial phase(AP)and post-vascular phase(PVP)images were used to observe whether there was hypervascularity and hypovascularity around the lesion.The expressions of heat shock protein 70(HSP70)and glypican 3(GPC3)in preoperative biopsy samples were detected by IHC method.Results When all CEUS indicators(AP,PVP)and IHC indicators(GPC3,HSP70)were diagnosed MVI individually,PVP had the highest diagnostic efficiency,with an accuracy of 91.0%and an area under the curve(AUC)of 0.893.The diagnostic efficiency of GPC3 combined with HSP70(accuracy:79.8%,AUC:0.790)was better than that of GPC3 alone(accuracy:69.5%,AUC:0.752)or HSP70 alone(accuracy:60.7%,AUC:0.701).The combined diagnosis of PVP+GPC3+HSP70 had the best diagnostic efficiency,with a specificity of 98.5%,an accuracy of 92.5%,and an AUC of 0.840.Conclusions Observing the PVP of CEUS and using IHC to detect the expressions of GPC3 and HSP70 can better diagnose the MVI of small HCC preoperatively.