Evaluation of Glypican-3 Expression in Non-Neoplastic, Preneoplastic and Neoplastic Liver Tissues, ANAN FATHI
Abstract
Background: Early detection of hepatocellular carcinoma (HCC) has become increasingly important as it has a poor prognosis and a high recurrence rate. It is considered as a major cause of morbidity and mortality. Therefore, it is helpful to use biomarkers that are specifically expressed in HCC. Glypican-3 (GPC3) is a promising diagnostic marker for hepatocellular carcinoma. It is an oncofetal protein that plays a role in the development and regulation of cellular proliferation and apoptosis. It has an established serologic and immunohis-tochemical diagnostic value for HCC, however its expression in smallhepatocellular carcinoma versus premalignant and benign liver lesions need further studies.
Aim: The aim of this study was to study the expression of Glypican-3 in cases of chronic hepatitis C with different grades of disease severity and hepatocellular carcinoma of different grades of differentiation. In addition to assessment of the diagnostic value of Glypican-3 in differentiating small hepatocellular carcinoma from small focal lesions.
Material and Methods: An immune-histochemical study using monoclonal antibody for glypican-3 was performed on paraffin sections of forty two specimens of liver tissues. They included thirty biopsies for chronic hepatitis C including twelve cirrhotic biopsies with macro nodules in six of them (3 benign regenerative nodules, 1 low grade dysplastic nodule, 2 high grade dysplastic nodules) and twelve biopsies for hepatocellular carcinomas including five small HCCs. They were collected from Pathology Departments of Zagazig Uni-versity Hospital and in Alahrar Hospital in the period between 2011-2013.
Results: In the current study glypican-3 was expressed in all cases (12/12) 100% of HCC with different grades as 3+ was noticed in (3/5) 60% of well differentiated HCC, (2/4) 50% of moderately differentiated HCC and in (3/3) 100% of poorly differentiated HCC. The pattern of expression was diffuse homogenous cytoplasmic and/or membranous staining. GPC3 was negatively expressed in (29/30) 96.7% of chronic hepatitis C biopsies including 3 benign regenerative nodules, 1 low grade dysplastic nodule and 1 high grade dysplastic nodule. One cirrhotic case (1/30) 3.3% with high grade activity and exhibiting high grade dysplastic nodule showed high (3+) diffuse granular cytoplasmic expression of GPC3. In small HCC, GPC3 was expressed in (5/5) 100% of cases however it was expressed in (1/2) 50% of high grade dysplastic nodules.
Conclusions: Glypican-3 is a diagnostic marker for HCC with different grades of differentiation. It can detect cirrhotic nodules with high risk of malignant transformation. In addition to its role in differentiating small hepatocellular carcinomas from small focal lesions.