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目的:探讨DKK-1、DKK-2和人磷脂酰肌醇蛋白聚糖3(glypican3,GPC3)蛋白在肝细胞癌组织中的表达及临床意义。方法:采用组织芯片联合免疫组织化学法检测DKK-1、DKK-2和GPC3蛋白在10例正常肝、12例肝硬化、57例肝细胞癌及癌旁肝组织中的表达差异,并分析其临床意义。结果:免疫组织化学检测结果发现,DKK-1和DKK-2在肝细胞癌组织中阳性染色率分别为59.65%(34/57)和57.89%(33/57);GPC3只在肝细胞癌组织中表达,其阳性染色率为47.37%(27/57),而在正常肝、肝硬化及癌旁肝组织中均呈阴性表达。DKK-1与DKK-2阳性表达之间存在密切相关性(χ2=0.570,P=0.000),DKK-2与GPC3阳性染色之间也存在相关性(χ2=0.272,P=0.041)。统计分析DKK-1、DKK-2及GPC3在肝细胞癌组织中阳性染色与肝癌患者性别、年龄、血清甲胎蛋白(α-fetoprotein,AFP)水平、乙肝表面抗原(hepatitis B surface antigen,HBsAg)、肿瘤大小、病理学分级、静脉浸润以及是否伴随肝硬化等的相关性,结果表明血清AFP水平与GPC3表达呈正相关(P=0.007),HBsAg与DKK-1表达呈正相关(P=0.037),DKK-1阳性染色与肝细胞癌组织分级存在相关性(P=0.014),与其他参数则无相关性。结论:GPC3在肝细胞癌组织的阳性染色率为47.37%,GPC3染色阴性的肝细胞癌组织中DKK-1和DKK-2双阳性染色率为40.00%,而GPC3(+)联合DKK-1(+)/DKK-2(+)/GPC3(-)可将肝细胞癌的免疫组织化学检出率提高至68.42%(39/57),降低肝癌免疫组织化学检测中的假阴性率。
Objective: To investigate the expression and clinical significance of DKK-1, DKK-2 and glypican3 (GPC3) in hepatocellular carcinoma. Methods: The expression of DKK-1, DKK-2 and GPC3 in 10 normal liver, 12 cirrhosis, 57 hepatocellular carcinoma and adjacent normal liver tissue were detected by tissue microarray combined with immunohistochemistry. Clinical significance. Results: Immunohistochemical results showed that the positive staining rates of DKK-1 and DKK-2 in hepatocellular carcinoma were 59.65% (34/57) and 57.89% (33/57), respectively. GPC3 only expressed in hepatocellular carcinoma , The positive staining rate was 47.37% (27/57), but negative in normal liver, cirrhosis and adjacent non-cancerous liver tissues. There was a close correlation between DKK-1 and DKK-2 positive expression (χ2 = 0.570, P = 0.000). There was also a correlation between DKK-2 and GPC3 positive staining (χ2 = 0.272, P = 0.041). The positive staining of DKK-1, DKK-2 and GPC3 in hepatocellular carcinoma was statistically analyzed with the gender, age, serum level of α-fetoprotein (AFP), hepatitis B surface antigen (HBsAg) (P = 0.007). The positive correlation between HBsAg and DKK-1 was found (P = 0.037). The correlation between serum AFP levels and the expression of GPC3 was significant There was a correlation between DKK-1 positive staining and histological grade of hepatocellular carcinoma (P = 0.014), but no correlation with other parameters. Conclusions: The positive staining rate of GPC3 in hepatocellular carcinoma was 47.37%, the positive staining rates of DKK-1 and DKK-2 in GPC3-negative hepatocellular carcinoma were 40.00%, while GPC3 (+) and DKK-1 +) / DKK-2 (+) / GPC3 (-) increased the immunohistochemical detection rate of hepatocellular carcinoma to 68.42% (39/57), and reduced the false negative rate in immunohistochemical detection of hepatocellular carcinoma.