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目的评价磷脂酰肌醇蛋白聚糖-3(GPC3)在血清甲胎蛋白(AFP)阴性乙型肝炎病毒(HBV)相关原发性肝细胞癌(hepatocellular carlinoma,HCC)中的诊断价值。方法应用免疫组织化学染色检测426例手术及179例肝穿刺活检的HBV相关HCC患者肝组织GPC3(GPC3L)的表达,并检测其血清AFP及血清GPC3(GPC3S)水平。结果 GPC3L可特异地表达于HCC细胞,而癌旁组织及肝硬化结节中无表达。手术切除的HCC组织中80.0%(341/426)为GPC3L阳性,且不同HCC分化程度之间GPC3阳性率差异无统计学意义(P>0.05)。穿刺活检的HCC组织中74.9%(134/179)为GPC3L阳性。AFP≥400μg/L对诊断HCC的敏感度为25.4%。AFP阴性和AFP≥400μg/L的HCC患者GPC3L阳性率分别为77.4%(328/424)和81.2%(147/181)。GPC3L和AFP无相关性。在AFP<400μg/L组GPC3S为(12.63±1.63)μg/L,在AFP≥400μg/L组为(20.20±2.11)μg/L,明显高于对照组的(1.92±0.32)μg/L,P<0.01。以GPC3Scut-off值为3.5μg/L,其在全部患者、AFP≥400μg/L和AFP阴性的HCC患者中的敏感度及特异度分别为54.6%和75.0%、54.6%和80.0%、80.0%和76.0%。结论 GPC3L可作为鉴别诊断AFP阴性HCC与肝硬化良性结节标志物,血清AFP与GPC3S的联合检测可提高HCC的早期诊断率。
Objective To evaluate the diagnostic value of glypican-3 (GPC3) in serum of patients with AFP-negative hepatocellular carinoma (HCC). Methods Immunohistochemical staining was used to detect the expression of GPC3L in liver tissues of 426 patients with HBV-related HCC and 179 patients with liver biopsy. The levels of serum AFP and serum GPC3 (GPC3S) were also detected. Results GPC3L was specifically expressed in HCC cells but not in paracancerous tissues and cirrhotic nodules. 80% (341/426) of the resected HCC tissues were positive for GPC3L, and there was no significant difference in the positive rate of GPC3 between the different degrees of HCC differentiation (P> 0.05). 74.9% (134/179) of the biopsied HCC tissues were GPC3L positive. The sensitivity of AFP≥400μg / L to diagnosis of HCC was 25.4%. The positive rates of GPC3L in AFP-negative and AFP≥400 μg / L HCC patients were 77.4% (328/424) and 81.2% (147/181), respectively. GPC3L and AFP no correlation. (12.63 ± 1.63) μg / L in AFP <400μg / L group and (20.20 ± 2.11) μg / L in AFP≥400μg / L group were significantly higher than those in control group (1.92 ± 0.32μg / L, P <0.01. The sensitivity and specificity of GPC3Scut-off value of 3.5μg / L were 54.6% and 75.0%, 54.6% and 80.0%, 80.0% in all patients, AFP≥400μg / L and AFP negative HCC patients respectively. And 76.0%. Conclusion GPC3L can be used as a differential diagnosis marker of AFP negative HCC and cirrhosis of benign nodules. Combined detection of serum AFP and GPC3S can improve the early diagnosis rate of HCC.