Differential Expression of Glypican-3 and Insulin–Like Growth Factor-II mRNAs and Alpha-fetoprotein and Ki-67 markers in Liver Tissues of HCV related Hepatocellular carcinoma in Egyptian Patients

Document Type : Research Articles


1 Theodor Bilharz Research Institute (TBRI), Giza, Egypt

2 National Hepatology and Tropical Medicine Institute (NHTMRI), Cairo, Egypt

3 National Cancer Institute, Cairo University, Cairo, Egypt


Background: Increasing evidence indicates that abnormal hepatocellular carcinoma (HCC) genes expression, such as glypican-3 (GPC-3) and insulin-like growth factor-II (IGF-II) were associated with the occurrence and progression of HCC. The objective of this study was to evaluate the differential expression of GPC-3 and IGF-II mRNAs in HCC tissues on top of Chronic hepatitis C virus (HCV) cirrhosis, in relation to Ki-67 and Alpha-feto protein (AFP) tissue markers expression.
Methods: One hundred and five patients, with HCC on top of Chronic HCV genotype 4 cirrhosis, who had undergone hepatectomy, were included, after obtaining informed consent. Total RNA extracted from malignant and corresponding peri-malignant liver tissues, and by reverse transcriptase-polymerase chain reactions (RT-PCR), the GPC-3 mRNA and IGF-II mRNA in addition to Beta-actin mRNA as internal control, were evaluated in all samples. Routine histopathological diagnosis as well as immunohistochemical (IHC) staining using monoclonal antibodies for Ki-67 and AFP were also done.
Result: The expression of GPC-3 mRNA was positive in all HCC malignant tissue, with overexpression in 86/105 (81.9%); in respect to the grade of the tumor(1-3 grades), while in peri-malignant tissue it was over expressed only in 20/105 (19%). The IGF-II mRNA was over expressed only in 10/105 (9.5%) in malignant and peri-malignant tissues. AFP was expressed in 33.3% of malignant samples and was absent in peri-malignant tissues. Ki-67 expression was significantly increased in malignant compared to peri-malignant tissue.
Conclusion: The GPC-3 and IGF II mRNA are good molecular markers for HCC, especially on top of cirrhosis due to chronic HCV infection. This was correlated significantly with the pattern of AFP and Ki-67 expression.


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