ORIGINAL ARTICLE: Expression pattern of glypican-3, HSP70, and glutamine synthetase in chronic hepatitis B and hepatocellular carcinoma

Soo Hee Kim, Kyoung Bun Lee, Hyeong-Ju Kwon, Ja-June Jang
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Abstract

Background and aim: The three-panel marker, glypican-3, HSP70 and glutamine synthetase, is helpful for making a diagnosis of early hepatocellular carcinoma. To further characterize the diagnostic values of these three markers, we performed immunostaining studies in non-neoplastic hepatocytes (chronic hepatitis B) and hepatocellular carcinoma. Methods: Immunostaining was performed for all three markers. The cases were 60 needle biopsies of chronic hepatitis B (30 with low-grade activity and 30 with high-grade activity) and 40 hepatocellular carcinomas (HCCs). Results: Glypican-3 staining was detected in only one of the 60 chronic hepatitis B cases, and this case expressed moderate immunoreactivity for glypican-3 and showed high-grade inflammatory activity. HSP70 expression was not observed in any cases. Glutamine synthetase was strongly immunoreactive at peri-venular hepatocytes with cytoplasmic staining in all cases. These findings reflected a normal expression pattern. On the other hand, all three markers were positive in 15 (37.5%) HCCs. At least two of three markers were positive in 26 (65.0%). Moreover, all three markers were negative in 2 (5.0%) HCCs. Conclusions: The combination of these three markers is highly specific for detecting hepatocellular carcinoma. However, caution should be exercised because non-neoplastic hepatocytes in chronic hepatitis B with high necro-inflammatory activity tend to show focal positivity for glypican-3. Also we emphasize that all three markers can show negative immunoreactivity in HCC.

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glypican-3、HSP70和谷氨酰胺合成酶在慢性乙型肝炎和肝细胞癌中的表达模式
背景与目的:glypican-3、HSP70和谷氨酰胺合成酶三组标志物有助于早期肝癌的诊断。为了进一步确定这三种标志物的诊断价值,我们在非肿瘤性肝细胞(慢性乙型肝炎)和肝细胞癌中进行了免疫染色研究。方法:对三种标志物进行免疫染色。其中60例为慢性乙型肝炎(30例为低级别活动性,30例为高级别活动性)和40例肝细胞癌(hcc)。结果:60例慢性乙型肝炎患者中仅有1例检测到Glypican-3染色,该病例对Glypican-3表现出中等免疫反应性,并表现出高度炎症活性。未见HSP70表达。在所有病例中,谷氨酰胺合成酶在静脉周围肝细胞的细胞质染色中表现出强烈的免疫反应。这些发现反映了正常的表达模式。另一方面,在15例(37.5%)hcc中,这三种标志物均为阳性。26例(65.0%)3种标志物中至少2种阳性。此外,2例hcc患者(5.0%)3种标志物均为阴性。结论:三种标志物联合检测肝癌具有较高的特异性。然而,应谨慎处理,因为慢性乙型肝炎的非肿瘤性肝细胞具有高坏死-炎症活性,往往显示glypican-3的局灶性阳性。我们还强调,这三种标志物在HCC中均可显示阴性免疫反应性。
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