Abstract
Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and thirdly leading cause of cancer-related death worldwide. The estimated risk of hepatocellular carcinoma is 15 to 20 times as high among persons infected with HCV as it is among those who are not infected, with most of the excess risk limited to those with advanced hepatic fibrosis or cirrhosis. Glypican3 (GPC3) plays a key role in relation to signaling with growth factors, regulating the proliferative activity of cancer cells. Glutamine synthetase (GS) catalyzes the synthesis of glutamine from glutamate and ammonia in the mammalian liver. GS was suggested as a specific marker for tracing cell lineage relationships during hepatocarcinogenesis. In normal liver, GS expression is seen in pericentral hepatocytes, but not by midzonal or periportal hepatocytes. In HCC, strong and diffuse GS expression in seen in tumor cells. Glypican3 immunopositvity was highly specific and sensitive indicator for hepatocellular carcinoma as well as glutamine synthetase which was found to be a sensitive and specific indicator for development of hepatocellular carcinoma when compared to cirrhosis, liver cell dyspalsia and metastatic carcinomas. Statistical analysis revealed a significant association between GPC3 and GS with tumor size (P=0.003, p=0.006, respectively). Diffuse staining significantly associated with large tumor size while, focal and mixed staining was detected more with small tumor size. Studying the relation with tumor grade also revealed significant association between diffuse GPC3 and GS staining with high tumor grade. Diffuse staining was detected in 91.7% and 100% respectively of poorly differentiated specimens and only in 33.3% and 22.2% of well differentiated specimens. While using GPC3 and GS to screen for premalignant hepatic lesions remains controversial, our data suggest that GPC3 and GS may be a reliable diagnostic immunomarkers to distinguish HCC from benign hepatocellular lesions. However, negative immunostaining should not exclude the diagnosis of HCC.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer, thirdly leading cancer-related death worldwide (Ismaeil et al, 2015)
The estimated risk of hepatocellular carcinoma is 15 to 20 times as high among persons infected with HCV as it is among those who are not infected, with most of the excess risk limited to those with advanced hepatic fibrosis or cirrhosis
Distinguishing hepatocellular carcinoma especially the well differentiated case from normal, cirrhotic liver tissue, liver cell dysplasia and liver metastatic carcinomas may be very difficult in some cases, in small needle core biopsies
Summary
Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer, thirdly leading cancer-related death worldwide (Ismaeil et al, 2015). It has a long latency, and most patients are often diagnosed at late stages when tumors are of high grade and progress rapidly (Weng et al, 2014). Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and thirdly leading cause of cancer-related death worldwide. In HCC, strong and diffuse GS expression in seen in tumor cells. Studying the relation with tumor grade revealed significant association between diffuse GPC3 and GS staining with high tumor grade. Negative immunostaining should not exclude the diagnosis of HCC
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