Upregulation of Glypican-3 expression in hepatocellular carcinoma but downregulation in cholangiocarcinoma indicates its differential diagnosis value in primary liver cancers (original) (raw)
Related papers
Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker
Biochemical and Biophysical Research Communications, 2003
With the global pandemic of hepatitis B and C infections, the incidence of Hepatocellular carcinoma (HCC) is rapidly increasing world wide. We identified glypican-3 (GPC3), a novel oncofetal gene over-expressed specifically in human HCC, as based on data of cDNA microarrays. As GPC3 is a GPI-anchored membrane protein and could be secreted, we attempted to detect secreted GPC3 protein in sera from HCC patients using Western blotting and ELISA. GPC3 protein was positive in sera of 40.0% (16/40) of HCC patients, and negative in sera from subjects with liver cirrhosis (LC) (0/13), chronic hepatitis (CH) (0/34), and healthy donors (0/60). All subjects were Japanese. Although 12 of 40 HCC patients were negative for both alpha-fetoprotein (AFP) and PIVKA-II well known tumor markers of HCC, four of these were GPC3-positive in the sera. We also observed vanishing GPC3 protein in the sera of three patients after the surgical treatment for HCC. On the other hand, immunohistochemical analysis revealed that HCC expressed GPC3 protein in all 14 HCC patients tested. In conclusion, GPC3, as defined in this study was shown to be a useful tumor marker for cancer-diagnosis for large numbers of patients with HCC.
Glypican-3 expression is correlated with poor prognosis in hepatocellular carcinoma
Cancer Science, 2009
The relationship between overexpression of glypican (GPC)-3 that is specific for hepatocellular carcinoma (HCC) and the prognosis has not yet been clarified. We attempted to determine the expression profile of GPC3 in association with the clinicopathological factors by immunohistochemical analysis in HCC patients and investigated the potential prognostic value of GPC3 by comparing the survival rate between the GPC3-positive and GPC3-negative HCC patients. Primary HCC tissue samples (n = 107) obtained from patients who had undergone hepatectomy between 2000 and 2001 were analyzed. GPC3 expression was less frequently observed in welldifferentiated HCC than in moderately and poorly differentiated HCC, the difference in the frequency being statistically significant. GPC3-positive HCC patients had a significantly lower 5-year survival rate than the GPC3-negative HCC patients (54.5 vs 87.7%, P = 0.031). Among 80 of the 107 (74.6%) patients with initial treatment who underwent hepatectomy, none of GPC3-negative HCC patients (n = 16, 20.0%) died during the follow-up period. No deaths were noted in the GPC3-negative HCC patients among the 71 (88.7%) patients with moderately and poorly differentiated HCC. Multivariate analysis identified GPC3 expression (P = 0.034) as an independent prognostic factor for the overall survival. We showed that GPC3 expression is correlated with a poor prognosis in
European Journal of Gastroenterology & Hepatology, 2022
Purpose: Hepatocellular carcinoma (HCC) is the seventh most common cancer all over the world and is second in cancer-related deaths.. In HCC, whose prognosis is still not good despite current treatments, there is a need for prognostic markers as well as early diagnosis. Glypican (GPC)-3 has been proposed as a potential serologic and histochemical marker speci c to HCC. The aim of this study was to determine the relationship between GPC3 overexpression and HCC prognosis and clinicomorphologic features. Patients and methods: In total 152 patients patients who were diagnosed as a result of hepatectomy, lobectomy, or liver transplantation were enrolled. The patients were divided into two groups as GPC3positive (>10%) and GPC3-negative (<10%). The demographic data of the patients ,tumor characteristics , survival times were recorded. Results: Survival was signi cantly lower in the GPC3+ group. In the multivariate analysis, hepatitis C, AFP, tumor number, tumor focality, portal vein tumor thrombosis, and GLP3 positivity were found to be independent risk factors on survival. Conclusion: Our study showing that GPC3 overexpression is a poor prognostic factor in HCC.GLP3 positivity were found to be independent risk factors on survival.
Carcinogenesis, 2015
Glypican-3 (GPC3) protein expression was determined by immunohistochemical analysis from 29 normal livers, 80 cirrhotic livers sample taken near hepatocellular carcinoma (HCC), and 87 cirrhotic livers without HCC. The levels for miR-657 and HCC-related gene mRNAs were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Also, a published microarray dataset was used for gene set enrichment analysis (GSEA) to investigate the relationship between GPC3- and HCC-related gene signatures. Kaplan-Meier analysis was used to evaluate the relationship between GPC3 and HCC recurrence. GPC3 protein expression was not detected in any of the 29 (0%) normal livers, but was detected in 32 of 87 (37%) cirrhotic livers without HCC, and 51 of 80 (64%) cirrhotic liver samples taken near HCC sites (P < 0.001). The GPC3-positive rate in cirrhotic livers of viral origin was 68% (27/40), which was significantly higher than for non-viral cirrhotic livers (11%, 5/47) (P < 0.001). Al...
Expression of glypican 3 in hepatoblastoma: an immunohistochemical study of 65 cases
Human Pathology, 2008
Glypican 3 is a heparin sulfate proteoglycan bound to the cell surface that is theorized to participate in cell signaling, resulting in embryonic cell growth and differentiation. The GPC3 gene is mutated in Simpson-Golabi-Behmel syndrome, whose features include numerous developmental abnormalities, tissue overgrowth, and an increased risk for embryonal malignancies, including hepatoblastoma. GPC3 has been detected in hepatic stem cells and was recently identified as one of the most overexpressed genes in hepatoblastoma by microarray analysis. The purpose of this study was to analyze the expression of GPC3 in a large series of hepatoblastoma using immunohistochemistry to assess its use as a diagnostic marker. The GPC3 immunoreactivity was semiquantitatively evaluated in 65 cases of hepatoblastoma. In addition, histologic patterns in each tumor were individually assessed for immunoreactivity. All 65 hepatoblastomas had cytoplasmic immunoreactivity for GPC3 with greater than 90% of cases showing strong, diffuse positivity. There was no reactivity in benign liver tissue. Fetal, embryonal, and small cell undifferentiated patterns were diffusely positive in almost all cases, whereas mesenchymal and teratoid patterns were nearly all negative. The high GPC3 expression consistently demonstrated in this study suggests that GPC3 may play a role in the tumorigenesis of hepatoblastoma.
Oncology Reports, 2017
Glypican-3 (GPC-3), a transmembrane heparan sulfate proteoglycan (HSPG), has recently been investigated as a player in tissue-dependent cellular signaling, specifically as a regulator of growth. Noteworthy, the regulatory protein has been implicated in both stimulatory and inhibitory pathways involving cell growth. Initially, GPC-3 was thought to act as a cell cycle regulator, as a loss-of-function mutation in the gene caused a hyper-proliferative state known as Simpson-Golabi-Behmel (SGB) overgrowth syndrome. Additionally, certain cancer types have displayed a downregulation of GPC-3 expression. More recently, the protein has been evaluated as a useful marker for hepatocellular carcinoma (HCC) due to its increased expression in the liver during times of growth. In contrast, the GPC-3 marker is not detectable in normal adult liver. Immunotherapy that targets GPC-3 and its affiliated proteins is under investigation as these new biomarkers may hold potential for the detection and treatment of HCC and other diseases in which GPC-3 may be overexpressed. Studies have reported that an overexpression of GPC-3 in HCC predicts a poorer prognosis. This prognostic value further pushes the question regarding GPC-3's role in the regulation and progression of HCC. This review will summarize the current knowledge regarding the clinical aspects of GPC-3, while also synthesizing the current literature with the aim to better understand this molecule's biological interactions at a molecular level, not only in the liver, but in the rest of the body as well. Due to the existing gap in the literature surrounding GPC-3, we believe further investigation of function, structure and domains, cellular localization, and other subfields is warranted to evaluate the protein as a whole, as well as its part in the study of HCC. Contents 1. Introduction and structure of GPC-3 2. Expression pattern of GPC-3 in human and mouse 3. GPC-3 as a serum marker for early detection of HCC 4. GPC-3 in resection, regeneration and liver diseases 5. GPC-3 as a therapeutic target for HCC 6. GPC-3 and co-receptors 7. Conclusion
Biosciences, Biotechnology Research Asia, 2016
Glypican-3 is a heparan sulfate proteoglycans (HSPGs) expressed at plasma membrane surface. Several studies demonstrated the re-expression of glypican-3 during the malignant transformation. Glypican-3 expression in hepatocellular carcinoma was suggested to be a diagnostic marker for differential diagnosis of hepatic nodules. The aim of the study is to evaluate the diagnostic value of glypican-3 as tumor marker not only in liver tumors but also in tumors of the other organs. A total of 95 surgically excised human tissues were subjected to immunohistochemical staining using a monoclonal antibody specific for glypican-3. These human tissues cover most of the common normal, benign, malignant and metastatic tumors originated from 27 anatomic sites. The immunohistochemical results revealed that glypican-3 was expressed in 17.4% of the normal tissues studied including stomach, small intestine, kidney (Normal cortex), and pancreas, while, the expression for glypican-3 was positive in 41.8 % of the benign and malignant tumors. The most frequent expressing tumor was hepatocellular carcinoma. Moreover, for the first time, several tumor entities showed glypican-3 expression including malignant meningioma, Hodgkin's lymphoma, B-non Hodgkin's lymphoma,T-non Hodgkin's lymphoma.
Annals of diagnostic pathology
Well-differentiated hepatocellular carcinoma (HCC) may be difficult to distinguish from a benign lesion. Glypican 3 (GPC-3) is an oncofetal protein, which has been demonstrated to be up-regulated in HCC. The aim of this study is to evaluate the diagnostic role of combined GPC-3 and CD34 immunoassaying in the distinction between HCC and benign hepatic mimickers. This study was performed on 100 cases of formalin-fixed, paraffin-embedded cases of hepatic focal lesions obtained from the files of pathology laboratory of our university from 2009 to 2012. The following groups were studied: group A (n = 60) (hepatocellular malignant lesions) and group B (n = 40) (Hepatocellular nonmalignant lesions). All cases were stained with GPC-3 and CD34. Sensitivity, specificity, and positive and negative predictive values were calculated for both antibodies. Glypican 3 and complete CD34 staining pattern expression in group A was significantly higher than in group B. The results of costaining showed t...
Glypican-3 in hepatocellular carcinoma
HCV infection patients without any complications, group III: 100 HCV infected patients complicated with cirrhosis and group IV: 150 HCV infected patients complicated with (90 localized and 60 metastatic) HCC. Detection of serum GPC3 and alpha-fetoprotein using an enzyme-linked immunosorbent assay (ELISA) were done to all subjects. Results: When analysis of variance was done between the four groups, a highly statistical significant difference was found between these groups regarding the mean serum levels of AFP and GPC-3 where the highest increase of three markers were found in the HCC group. The combined AFP and Glypican-3 improve the sensitivity and specificity of AFP alone. Conclusions: GPC-3 could be a sensitive, specific and accurate marker for early detection of HCC diagnosis.