Glypican-3 in hepatocellular carcinoma (original) (raw)
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2018
This work aimed to set-up and evaluate a lab-made immunoradiometric assay for the detection of plasma glypican-3 (GPC3) in comparison with a commercial ELISA kit and to use them to evaluate the diagnostic potential of GPC3 in HCC patients. Anti-GPC3 monoclonal antibodies were radioiodinated and used with a second antibody in the IRMA assay. The study included 450 subjects in 3 groups, 150 HCC patients, 150 hepatitis-C-virus (HCV) patients and 150 normal healthy subjects. Plasma GPC3 was assayed by our lab-made IRMA and by a commercial ELISA kit, along with alpha-fetoprotein (AFP). We were able to set-up an IRMA assay to measure plasma GPC3 and applied it to diagnose HCC patients. When compared to a ELISA kit, our IRMA assay showed much better performance characteristics on ROC curves with much higher area under the curves, sensitivities and specificities when diagnosing HCC patients from normal controls or HCV patients. Using our IRMA assay, showed that GPC3 is a good diagnostic ind...
Afro-Egyptian Journal of Infectious and Endemic Diseases
Background and study aim: Glypican-3 (GPC3) is common kind and new type of the Glypicans group. These groups were connected to the epithelial cell membrane by a glycosyl-phosphatidylinositol bond. These proteins control the signaling action of various growth factors, especially Wnts. This reaction is predicated on the power of glypican to initiate, promote or suppress the reaction of these growth agents with their interactive signaling receptors. It is obviously proven and documented that GPC3 is secreted and released by most malignant liver cells, this glypican is not isolated from healthy hepatocyte, cirrhotic liver cells , or in even in benign liver masses. GPC3 accelerates the development of malignant liver lesions especially HCC by stimulating canonical Wnt impulses. The study aimed to characterize and assess the diagnostic accuracy of serum glypican-3 (GPC3) in early detection of HCC in cirrhotic patients and could be used as good screening marker for HCC in cirrhotic patients instead of AFP. Patients and Methods: We enrolled 60 patients which divided into 2 groups, group1 which included 30 patients diagnosed to have HCC and group 2 which included 30 patients diagnosed to have liver cirrhosis. Results: Our results revealed increased levels of Glypican-3 in hepatoma group and liver cirrhosis group with no significant difference (p=0.3). Conclusion: Serum GPC3 is not an efficient immune-marker for HCC that can be used alone to differentiate HCC from benign hepatic focal lesions, particularly hepatocellular adenoma.
The Egyptian Journal of Hospital Medicine
Background: Hepatocellular carcinoma is a highly prevalent tumor globally and the world's second leading cause of cancer-related deaths. Glypican-3, a heparan sulfate proteoglycan expressed on the surface of HCC cells, has emerged as a new molecule with a strong link to occurrence and progression of HCC. Objective: This study was done to determine the role of Glypican-3 in diagnosis of HCC and its prognostic value following different treatment modalities. Patients and methods: The study included thirty patients with liver cirrhosis and HCC on top, and thirty patients with liver cirrhosis without HCC. Standard laboratory investigations, abdominal ultrasound and triphasic computed tomography were done for all patients. Serum alpha fetoprotein and Glypican-3 were measured in all patients before and one month after different treatment modalities. Results: Glypican-3 was significantly higher in HCC group (2.28 ± 0.97) in comparison to cirrhosis group (0.56 ± 0.31) with P-value <0.001. Glypican-3 level was higher in larger sized lesions with p value 0.023, one month after treatment with different modalities, Glypican-3 declined significantly (from 2.28 ± 0.97 to 1.44 ± 0.93) with p value <0.001. At a cutoff point of > 1.1 ng/ml Glypican-3 has 93.3% sensitivity, 96.67% specificity, 96.6% PPV and 93.5% NPV for detection of HCC. Conclusion: Glypican-3 can be a valuable diagnostic marker for HCC diagnosis and prognosis after various treatment modalities and may be complementary to alpha fetoprotein increasing overall sensitivity of HCC detection.
Diagnostic Value of Glypican-3 for Hepatocellular Carcinomas
Asian Pacific journal of cancer prevention : APJCP, 2018
Background: Hepatocellular carcinoma (HCC) is a common and dangerous malignancy in many parts of the world, and especially in Egypt. Early diagnosis is the most important step in successful HCC management. However most cases are detected at late stage making effective intervention impossible. Aim: The aim of this study was to evaluate the potential of Glypican-3 (GPC-3) to aid in diagnosis of HCC, especially in patients with low serum alpha-fetoprotein (AFP). Subjects and methods: Serum GPC-3 was assessed by flow-cytometry and serum AFP by enzyme-linked immunosorbent assay (ELISA) in 40 HCC patients with AFP< 400ug\l. (GI), 40 HCC patients with AFP> 400ug\l. (GII) and 20 healthy controls (GIII). Results: GPC-3 was found to be significantly elevated in HCC as compared to healthy subjects (GI 38.2±22. 5, GII 50.2±22.6, and GIII 2.24±1.19), with sensitivities of 85% for GI and 84% for GII and specificities of 95% for GI and 92% for GII. AFP showed respective sensitivities of 50% ...
Tumor Biology, 2016
Conflicting results for circulating glypican-3 (GPC3) were reported in hepatocellular carcinoma (HCC) diagnosis. We aimed to improve the diagnostic power of GPC3 by developing a GPC-HCC model for diagnosing HCC. GPC3 was tested for HCC (138), liver cirrhosis (56), and fibrosis (62) patients by ELISA. Data from patient groups were retrospectively analyzed. A novel score, GPC-HCC, based on combination of GPC3 and routine laboratory tests, was developed for HCC diagnosis. The GPC-HCC model values produced a significant 1.7-fold increase in liver cirrhosis and 3.2-fold increase in HCC, in comparison with liver fibrosis. In contrast to GPC3 and alpha fetoprotein (AFP), the GPC-HCC model showed high HCC diagnostic power with area under the curve (AUC) of 0.939, sensitivity 93 %, specificity 93 %, positive predictive value 89 %, negative predictive value 95 %, and efficiency 93 %. GPC-HCC AUC in HCC with single tumor, absent vascular invasion, and tumor size ≤3 cm were 0.93, 0.92, and 0.92, respectively, compared with 0.63, 0.63, and 0.64, respectively, for GPC3 and 0.69, 0.70, 0.55, respectively, for AFP. In conclusion, owing to these promising findings, the combination of GPC3 with other laboratory simple routine tests (GPC-HCC model) could improve the diagnostic power of GPC3 in HCC screening and follow up of cirrhotic patients.
Role of Serum GLYPICAN-3 (GPC-3) in Early Detection of Hepatocellular Carcenoma
Al-Azhar Medical Journal, 2015
Background The false negative rate of alpha-fetoprotein (AFP) level alone may be as high as 40% for patients with early stage of hepatocellular carcinoma (HCC) and may be elevated in non-malignant chronic liver diseases and other malignancies. Glypican-3 (GPC-3) is a new tumor marker for HCC. Objective: Evaluation of the role of serum GPC-3 in the early diagnosis of HCC. Results: There was a highly significant difference between control and HCC group as regard AFP and serum GPC-3. There was a highly significant difference between liver cirrhosis and HCC group as regard AFP and serum GPC-3. No significant difference between control and liver cirrhosis groups as regard AFP and GPC-3. AFP showed sensitivity (75%), specificity (63%), positive predictive value (PPV) (62.8%) and negative predictive value (NPV) (69.9%) at cutoff value 195ng/ml for HCC group. Serum GPC-3 showed sensitivity of (87%), specificity of (95%), PPV of (93.8%) and NPV of (91.2%) at cutoff 5.1ng/ml for HCC group. Combined serum GPC-3 and AFP showed sensitivity (85.9%), specificity (88%) PPV (85.4%) and NPV (84.1%) at cut of value 5.1 ng/ml and 195 ng/ml respectively for HCC group. No significant correlation of serum GPC-3 or AFP to the tumor size, number or vascular invasion in HCC group. Conclusion: GPC-3 is a promising diagnostic marker with high sensitivity and specificity for HCC than AFP in detection, screening HCC and follow up treatment of HCC.
AIM: The distinction of hepatocellular carcinoma (HCC) from the metastatic carcinoma (MC) and intrahepatic cholangiocarcinoma (CC) often presents a diagnostic challenge that carries a significant impact on its subsequent management. In this study we aimed to evaluate the immunohistochemical expressions of arginase-1, hepatocyte paraffin antigen-1 (HepPar-1), and glypican-3 (GPC-3) in a trial to distinguish HCC from non-HCC involving the liver. MATERIALS AND METHODS: The study included 64 cases (32 HCC, 28 MC and 4 CC) and 5 specimens of normal liver tissues. These cases were investigated retrospectively from the archive of the Pathology Department, Zagazig University Hospitals. The predictive capacity of arginase-1, HepPar-1 and GPC-3 staining was determined using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) calculations. RESULTS: Both arginase-1 and HepPar-1 expressions were present in all cases of non-neoplastic hepatocellular tissues, whereas GPC-3 expression was absent in all cases. Only two of 28 (7.1%) cases of MC and one of 4 (25%) cases of CC showed positive immunoreactivity for arginase-1. HepPar-1 immunoreactivity was detected in 3 of 28 (10.7%) cases of MC and in one of 4 (25%) cases of CC. GPC-3 immunoreactivity was detected in 2 of 28 (7.1%) cases of MC and negative in all cases of CC. Arginase-1 was more sensitive (87.5%) than HepPar-1 (71.9%) or GPC-3 (65.6%) for HCC. GPC- 3 was more specific (93.8%) than HepPar-1 (87.5%) and arginase-1 (90.6%). However, the combination of the three biomarkers for the diagnosis of HCC raised the specificity to 100%. CONCLUSION: Arginase-1 and HepPar-1 are effective biomarkers for HCC differentiation. Also, arginase-1 demonstrates a superior sensitivity in comparison with GPC-3 and HepPar-1 in the diagnosis of HCC, whereas GPC-3 demonstrates superior specificity. Hence, the use of combination of arginase-1 with HepPar-1 and GPC-3 could be useful in the precise diagnosis of HCC and distinguishing it from non-HCC.
Journal of the Egyptian National Cancer Institute, 2013
Evaluation of the sensitivity and specificity of glypican3 (GPC3) in differentiating hepatocellular carcinoma (HCC) from metastatic carcinomas of the liver in cell block material. Patients and methods: Sixty cell blocks were prepared from liver FNAs performed in the radiodiagnosis department, National Cancer Institute, in the period between August 2011 and May 2012. Cases diagnosed as hepatocellular carcinoma, or metastatic carcinoma were included in the study. Cell block sections were stained with anti GPC-3. Sensitivity, specificity, and positive and negative predictive values, of GPC3 were calculated. The final diagnosis was based on the triple approach of clinical data, radiological findings, as well as cytomorphologic features aided by GPC-3 results. Results: 70% of cases were diagnosed as HCC, and 30% as metastatic carcinomas. 95.2% of HCC cases expressed GPC3. Poorly differentiated cases showed the highest GPC3 sensitivity (100%), followed by moderately differentiated cases (96.5%), while well differentiated cases expressed GPC3 in 90% of cases. 83.3% of metastatic carcinomas were negative for GPC3. In this study, sensitivity of GPC-3 in HCC was 95.2%, specificity was 83.3%, positive and negative predictive values were 93% and 88.2% respectively, and total accuracy was 91.7%. Conclusion: Immunocytochemical staining for GPC3 in cell block material is a highly sensitive and specific method capable of distinguishing HCC from the vast majority of metastatic carcinomas of the liver.
Can Glypican3 be diagnostic for early hepatocellular carcinoma among Egyptian patients?
Asian Pacific journal of cancer prevention : APJCP, 2013
Because of the high prevalence of hepatocellular carcinoma (HCC) in Egypt, new markers with better diagnostic performance than alpha-feto protein (AFP) are needed to help in early diagnosis. The aim of this work was to compare the clinical utility of both serum and mRNA glypican3 (GPC3) as probable diagnostic markers for HCC among Egyptian patients. A total of 60 subjects, including 40 with HCC, 10 with cirrhosis and 10 normal controls were analyzed for serum GPC3 (sGPC3) by ELISA. GPC-3 mRNA from circulating peripheral blood mononuclear cells was amplified by RT-PCR. Both markers were compared to some prognostic factors of HCC, and sensitivity of both techniques was compared. Serum glypican-3 and AFP were significantly higher in the HCC group compared to cirrhotic and normal controls (p<0.001). Sensitivity and specificity were (95% each) for sGlypican-3, (82.5% and 85%) for AFP, and (100% and 90%) for Glypican3 mRNA , and (80% and 95%) for double combination between sGPC3 and AF...