Clinical-liver, pancreas, and biliary tractGlypican-3: a novel serum and histochemical marker for hepatocellular carcinoma☆
Section snippets
Patient tissues
Liver tissue samples were obtained from the Department of Pathology at Toronto General Hospital. All liver specimens were large blocks from surgically resected tumors and adjacent parenchyma. All tissue was fixed in 10% formalin and embedded in paraffin for routine histologic examination.
Patient sera
Blood samples were obtained from 34 patients with HCC (see Table 1 for patient characteristics), 20 patients with hepatitis plus liver cirrhosis (12 with hepatitis C virus and 8 with hepatitis B virus; 17 with
Generation of anti-GPC3 mouse mAbs
To generate the antibodies, we used a His-tagged carboxyl-terminal GPC3 fragment as immunogen. After screening the hybridomas by ELISA against the immunogen without the His tag, 13 positive clones were selected. The positive clones were then tested by immunostaining GPC3-transfected 293 cells. Two stable hybridoma clones, named 1G12 and 8H5, immunostained the GPC3-expressing cells in a strong and specific manner (Figure 1). Because both antibodies displayed similar reactivity, we chose the
Discussion
By immunostaining paraffin-embedded tissue sections with an mAb, we have shown that GPC3 is expressed in 72% of HCCs, whereas it is undetectable in hepatocytes from benign liver diseases, reactive liver, and normal liver. These results are consistent with the 2 previous studies that assessed the levels of GPC3 mRNA in HCC and nonmalignant hepatic tissue18, 19 and suggest that GPC3 could be a useful immunohistochemical marker to distinguish between benign and malignant hepatocellular mass
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M.C. is supported by a fellowship from the Cancer Research Society of Canada.