| Hepatocellular carcinoma (HCC) is the sixth most common cancer, and characterized by high mortality, frequent postsurgical recurrence and extremely poor prognosis. Therefore, early diagnosis should play an important role in ameliorating the prognosis in patients with HCC. Although the early detection of nodular lesions in cirrhotic liver increased under the imaging techniques recently, it was still difficult to confidently distinguish small hepatocellular carcinomas from precancerous high-grade dysplastic nodules and benign focal lesions based on imaging findings alone in a considerable number of cases. Up to date, alpha fetal protein (AFP) as a biomarker is applied widely in diagnosis of HCC, but its sensitivity is only 60%-70%. Several studies have demonstrated that Glypican-3 (GPC3) was a promising tumor marker because of its high sensitivity and specificity. Here the expression of GPC3 was investigated in HCC, peritumor tissues, dysplastic nodules, cirrhosis and chronic hepatitis, compared with tissues in healthy controls.AIM:To analyze the expression of GPC3 in various liver tissues including hepatocellular carcinoma, dysplastic nodules, and its significance in the early diagnosis and differential diagnosis of hepatocellular carcinoma.METHODS:The expressions of GPC3 and AFP were detected by immunohistochemical (IHC) in 126 thin core biopsy specimens (including 57 HCC in early stage,16 dysplastic nodules,29 liver cirrhosis and 24 hepatitis) and 57 HCC resected samples in intermediate and advanced stage and 28 resection normal liver tissues as control group. Meanwhile GPC3 mRNA was investigated by quantitive RT-PCR (qRT-PCR) in situ containing paired intratumoral and peritumoral tissues from 100 patients with HCC,25 cirrhotic patients and 15 healthy controls.RESULTS:(1) The results of GPC3 from IHC:The expression of GPC3 in HCC differed significantly from those in other five kinds of tissue samples (P<0.01). GPC3 showed higher diagnostic sensitivity (80.7%) and specificity (99.4%) than that of AFP (37.7% and 93.6%, respectively). GPC3 and AFP of liver cirrhosis and chronic hepatitis displayed negative IHC staining. The positive staining of GPC3 was found in 77.2% samples in HCC with early stage, and the expression of GPC3 in early stage was significantly higher than that in high-grade dysplastic nodules (P<0.01). The positive staining of GPC3 was detected in 78.6% samples, but IHC positive for GPC3 combined with AFP increased to 85.7% in the patients with small HCC. The GPC3 showed positive IHC staining in 70% small HCC samples which serum AFP was less than 20μg/L. (2) The results of GPC3 mRNA:Quantitve RT-PCR indicated that the expression of GPC3 mRNA (median, IQR) was either low or absent in normal liver (1.13,0.80-1.40), in cirrhosis (3.32,1.58-4.81), and in peritumor (1.73,0.55-3.96). In contrast, the expression of GPC3 mRNA was markedly increased in 88 of 100 (88%) HCC samples (97.01,16.54-328.5) compared with each of the above liver tissues (P<0.01). Additionally, the increase in GPC3 mRNA expression in HCC with early stage (90.9%) was similar with expression in HCC with intermediate and advanced stage (87.2%). GPC3 mRNA highly expressed in 84.5%(49/58) HCC with AFP<400μg/L and in 88.2%(15/17) early stage HCC with serum AFP negative.CONCLUSIONS:GPC3 is markedly overexpressed in HCC compared with normal liver, liver cirrhosis or displasia. Moreover, GPC3 has high sensitivity and specificity in HCC with early stage. These findings suggest that GPC3 may serve as a novel marker for early diagnosis in HCC. Immunohistochemistry for GPC3 in liver thin core biopsy specimens is an effective ancillary tool in the early diagnosis and differential diagnosis of hepatocellular carcinoma. |
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