GPC3对AFP阴性乙型肝炎病毒相关肝细胞癌的诊断价值

Diagnostic value of glypican-3 in patients with alpha fetoprotein negative hepatitis B related hepatocelluar carcinoma

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 patients with alpha fetoprotein （AFP） negative hepatitis B related hepatocellular carcinoma （HCC）. Methods The expression of GPC3 in liver tissue （GPC3L）was tested by immunohistochemistry staining from 426 tissues for surgery and 179 needle biopsy tissues of hepatitis B related HCC patients, serum GPC3 （GPC3S） and AFP were also measured. Results GPC3L was easily detected to be expressed in HCC specific cells, and no expression in paracarcinomatous and cirrhotic nodules tissues. It was found GPC3L was positive in 80.0% （341/426） of tissue samples got from surgery. There was no significant difference of the GPC3L expression among HCC differentiation degree （P 〉 0.05）. GPC3L was positive in 74.9% （134/179） of needle biopsy tissues from HCC patients. The sensitivity of serum AFP≥400 μg/L for diagnosis HCC was 25.4%. The GPC3L expression was detected in 77.4% （3281424） of patients with serum AFP negative and in 81.2% （147/181） of patients with AFP≥400 μg/L. There was no relationship between GPC3L and AFP. The mean of GPC3S in patients with AFP〈400 μg/L [（12.63± 1.63）μg/L] or AFP≥400 μg/L [（20.20±2.11）μg/L] was significantly higher than that in the control group[ （1.92~0.32）μg/L], P 〈 0.01. The cut-off value of GPC3S was 3.5 μg/L to determine HCC as a positive. The sensitivity and specificity in all, AFP≥400 μg/L and AFP negative HCC patients were 54.6% and 75.0%, 54.6% and 80.0%, 80.0% and 76.0%, respectively. Conclusion GPC3 may be helpful in improving diagnosis of HCC and in differentiating diagnosis between AFP negative HCC and cirrhotic nodules.