Expression of glypican-3 is highly associated with pediatric hepatoblastoma: a systemic analysis.

Xiao-Li Xiong,Su-Qi Yan,Huan Qin,Peng Chen,Li-Shan Zhou,Dong-Chi Zhao

doi:10.7314/apjcp.2015.16.3.1029

Abstract

Glypican-3 (GPC3) is reported to be an oncofetal protein that is a useful diagnostic immunomarker for hepatoblastoma. However, the results are not inclusive. This study systemically investigated the association between expression of GPC3 and pediatric hepatoblastoma. Clinical studies evaluating the association were identified using a predefined search strategy. GPC3 immunohistochemistry was applied in the pathological diagnosis of hepatoblastoma using the monoclonal antibodies with formalin-fixed and paraffin-embedded specimens. Positive predictive rates for the association between expression of GPC3 and pediatric hepatoblastoma were calculated. Specimens from four clinical studies which including 134 patients with pediatric hepatoblastoma tested by GPC3 immunohistochemistry were considered eligible for inclusion. Systemic analysis showed that, in all patients, pooled positive predictive rate of the association between expression of GPC3 and pediatric hepatoblastoma was 95.5% (128/134). This systemic analysis suggests that the expression of glypican-3 is highly associated with the diagnosis of pediatric hepatoblastoma.

Highlights

Hepatoblastoma is one of the most common primary cancers in children and accounts for two-thirds of all malignant liver neoplasms in children (Ismail et al, 2012)
Characteristics of studies included in the analysis are presented as these outcomes: GPC3 was positive in fetal epithelial cells (54/54, 100%), Nonneoplastic hepatocytes adjacent to tumor were negative for GPC3 expression (0/10) of Wang, et al.; GPC3 expression was seen in 9/9 (100%) hepatoblastomas of Chan et al.; All 65 hepatoblastomas had cytoplasmic immunoreactivity for GPC3 with greater than 90% of cases showing strong, diffuse positivity of Zynger et al.; and Diffusely positive staining of GPC3 was observed in malignant hepatocytes in hepatoblastomas and in hepatocellular carcinomas (47/56, 84%) of Yamauchi et al Totally, specimens from four clinical studies which including 134 patients with pediatric hepatoblastoma tested for GPC3 were included
GPC3 is a member of the glypican family of glycosylphosphatidyl inositol-anchored cell-surface heparan sulfate proteoglycans (Filmus et al, 2001)

Summary

Introduction

Hepatoblastoma is one of the most common primary cancers in children and accounts for two-thirds of all malignant liver neoplasms in children (Ismail et al, 2012). Reticulin staining and (more recently) CD34-immunohistochemistry have been recognized as helpful diagnostic markers in differential diagnoses among hepatic lesions (hepatocellular carcinoma, dysplastic nodules, and other benign hepatocellular lesions), their clinical effectiveness is still somewhat not clear (Park et al, 1998; Kong et al, 2000) Another difficult challenge in the diagnosis of hepatocellular carcinoma is the differentiation from primary hepatic cholangiocellular carcinoma and liver metastases. While studies on ovarian cancer cell lines, mesotheliomas, and breast tumors have demonstrated the down regulation of GPC3 (Lin et al, 1999; Murthy et al, 2000; Xiang et al, 2001), other investigations on hepatocellular carcinoma have shown a marked elevation of GPC3 mRNA over the level observed in corresponding normal tissues (Hsu et al, 1997; Lage et al, 1998; Saikali et al, 2001; Zhu et al, 2001) On this background, we hypothesize that GPC3 could be associated with the clinical manifestation of pediatric hepatoblastoma

Methods

Results

Conclusion