HSP70、GPC3、GS和AKR1B10在肝脏高度异型增生结节免疫组化诊断中的应用

Application of HSP70,GPC3,GS and AKR1B10 in immunohistochemical diagnosis of highgrade dysplastic nodule of liver

目的探讨免疫组化标志物热休克蛋白70(heat shock protein 70,HSP70)、磷脂酰肌醇蛋白聚糖3(glypican 3,GPC3)、谷氨酰胺酶(glutamine synthetase,GS)和正醛酮还原酶家族中单分子醛糖还原酶(aldo-ketoreductase family 1 member B10,AKR1B10)在肝脏高度异型增生结节(high-grade dysplastic nodule,HGDN)和高分化小肝细胞癌(well-differentiated small hepatocellular carcinoma,WD-SHCC)中的表达特点及鉴别诊断价值。方法对16例单结节型HGDN和32例WD-SHCC进行HSP70、GPC3、GS和AKR1B10免疫组化染色。结果 4项标志物在HGDN与WD-SHCC组织中均可表达,单项标志物中,HSP70在HGDN与WD-SHCC中阳性率最高(31.25%,81.25%,P<0.001);GPC3在HGDN与WD-SHCC中阳性率最低(12.50%,25.00%,P<0.460)。HSP70+GPC3+GS及HSP70+AKR1B10+GS诊断组合均在3项标志物中至少2项阳性时,获取最佳诊断效果,此时诊断敏感性和准确率分别为62.50%、81.25%和70.83%、83.33%,特异性均为87.50%。结论HSP70、GPC3和GS经典免疫组化诊断谱对HGDN和WD-SHCC组织具有一定的鉴别能力。然而,GPC3在WD-SHCC中阳性率较低,表达水平与HGDN无明显差异,制约该谱的整体诊断效果。AKR1B10替代GPC3后,在维持较高特异性一致的同时,可明显提高诊断敏感性和准确率。

Purpose To explore the expression characteristics and differential diagnostic value of heat shock protein 70 （ HSP70）, glypican 3 （GPC3）, glutamine synthetase （GS） and aldo-ketoreductase family 1 member B10 （AKR1B10） between high-grade dys- plastic nodule （HGDN） and well-differentiated small hepatocellular carcinoma （WD-SHCC）. Methods Immumohistochemical stai- ning of HSP70, GPC3, GS and AKR1BIO was performed on 16 uninodular HGDN and 32 WD-SHCC. Results All of 4 immunohisto- chemical markers expressed in HGDN and WD-SHCC. HSP70 had the highest positive rate with 31.25% and 81.25% in HGDN and WD-SHCC （P 〈0. 001 ）, and the lowest was GPC3 with 12. 50% and 25.00% （P 〈 O. 460）, respectively. When at least 2 of 3 markers were positive, the immumohistochemical combinations of HSP70 ＋ GPC3 ＋ GS and HSP70 ＋ AKR1B10 ＋ GS both showed the best diagnostic performances with a consistent diagnostic specificity of 87.50%. The diagnostic sensitivities and accuracies were 62. 50% vs 81.25% and 70. 83% vs 83.33%. Conclusion The immumohistoehemieal combination, GPC3, HSP70 and GS, is a significantly differential diagnostic panel for HGDN and WD-SHCC, but GPC3 has inadequate positive rate, which reduces the diagnostic effectiveness of this panel. AKR1B10, a replacement of GPC3, could significantly improve the diagnostic sensitivity and accuracy with a consistent specificity.