Preliminary study of three tumor markers for hepatocellular carcinoma: AFP, AFP-L3, and Glypican-3

Abstract

15014 Background: a-Fetoprotein (AFP) is the most widely used biochemical marker for detection of hepatocellular cancer (HCC). AFP is also elevated in acute and chronic liver disease, limiting its utility as an early indicator of HCC. Recently, AFP-L3 and glypican 3 (GPC3) have been reported for early detection of HCC. AFP-L3 is a glycoform of AFP produced by malignant liver cells. Measurement of AFP-L3 as a percentage of total AFP helps distinguish non-malignant hepatic disease from HCC. GPC3 is a heparin sulfate proteoglycan anchored to the plasma membrane. The level of GPC3 in the serum of HCC patients is higher than in the serum of healthy adults or patients with non-malignant hepatopathy. We tested the concordance of AFP, AFP, AFP-L3%, and GPC3and GPC3 to determine if their simultaneous measurement may increase the sensitivity of identifying individuals at risk for HCC. Method: De-identified clinical samples (n = 176) submitted for AFP-L3% measurement were tested. AFP and AFP-L3 levels were measured using the LiBASys automated analyzer (Wako Chemicals USA Inc, Richmond, VA). GPC3 levels were measured with a commercial ELISA kit (BioMosaics, Inc, Burlington, VT). To assess concordance we categorized results according to accepted cut-off values for AFP and AFP-L3, and a clinically established reference range for GPC3. Results: Fourteen of the 176 samples had elevated GPC3 (=180pg/mL), 6 (43%) of which had normal AFP values (<20ng/mL). Forty- seven of the 176 samples had elevated AFP-L3% (L3 =10%), 6 (12.8%) of which had normal AFP levels. Conclusion: These data suggest that GPC3 and AFP-L3% may be used as supplemental markers, and the simultaneous determination of AFP, AFP-L3, and GPC3 may provide a higher sensitivity for identifying individuals with increased risk of HCC. [Table: see text] No significant financial relationships to disclose.