Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma.
OBJECTIVE
Early detection of hepatocellular carcinoma (HCC) is critical for successful treatment. However, the differential diagnosis between HCC and benign hepatic lesions is sometimes difficult and new biochemical markers for HCC are required. It has been reported that glypican-3 (GPC3) messenger RNA (mRNA) is significantly increased in most HCCs compared with benign liver lesions or normal liver. The goal of this study is to determine whether GPC3 is also overexpressed at the protein level and whether GPC3 is detectable in the serum of patients with HCC.


METHODS
GPC3 was assessed in liver tissue sections by immunohistochemistry and in serum by enzyme-linked immunosorbent assay. Serum alpha-fetoprotein (AFP) level was also measured in the same patients.


RESULTS
Immunohistochemical studies showed that GPC3 is expressed in 72% of HCCs (21 of 29), whereas it is not detectable in hepatocytes from normal liver and benign liver diseases. Consistent with this, GPC3 was undetectable in the serum of healthy donors and patients with hepatitis, but its levels were significantly increased in 18 of 34 patients (53%) with HCC. In addition, only 1 of 20 patients with hepatitis plus liver cirrhosis displayed elevated levels of serum GPC3. Interestingly, in most cases, there was no correlation between GPC3 and AFP values. Thus, at least 1 of the 2 markers was elevated in 82% of the patients with HCC.


CONCLUSIONS
GPC3 is specifically overexpressed in most HCCs and is elevated in the serum of a large proportion of patients with HCC. The simultaneous determination of GPC3 and AFP may significantly increase the sensitivity for diagnosis of HCC.
Capurro
Mariana
M
Division of Molecualr and Cell Biology, Sunnybrook and Women's College Health Sciences Center and Deaprtment of Medical Biophysics, University of Toronto, Ontario, Canada.
Wanless
Ian R
IR
Sherman
Morris
M
Deboer
Gerrit
G
Shi
Wen
W
Miyoshi
Eiji
E
Filmus
Jorge
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000473:pathology*; D005260:Female; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans / Q000032:analysis* / Q000097:blood / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008113:Liver Neoplasms / Q000737:chemistry / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000378:metabolism
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans; D000509:alpha-Fetoproteins