Diagnostic value of glypican-3 in serum and liver for primary hepatocellular carcinoma

Abstract

Aim: To evaluate the diagnostic value of glypican-3 (GPC3) in serum and liver for primary hepatocellular carcinoma (HCC).

Methods: Serum levels of GPC3 and α-fetoprotein (AFP) were measured in 75 patients with primary HCC and 32 patients with liver cirrhosis. Expression of GPC3 and AFP in 58 HCC and 12 cirrhotic specimens was detected with immunohistochemical staining.

Results: When the cut-off value of serum GPC3 was set at 300 ng/L, its sensitivity and specificity for HCC were 47.0% and 93.5%, respectively. Among the 14 patients with HCC at stage according to the Barcelona Clinic Liver Cancer staging system, the serum GPC3 level was higher than 300 ng/L in 50% (7/14) patients, the serum AFP level was not ≥ 400 μg/L in any patient. Combined serum AFP and GPC3 significantly increased the sensitivity to the diagnosis of HCC. The GPC3 expression was detected in cytoplasm of HCC cells but not in hepatocytes and bile ducts of benign tumors. Among the 58 HCC patients, the GPC3 was expressed in 100% (28/28) patients with their serum AFP level ≥ 400 μg/L, and in 90% (27/30) patients with their AFP level < 400 μg/L, respectively. The GPC3 was weakly or negatively expressed in all paracarcinomatous and cirrhotic tissue samples. AFP positive HCC cells were only found in 1 out of the 58 HCC patients.

Conclusion: GPC3 protein is a sensitive and specific serum marker for diagnosis of early HCC. Its expression in liver tissues can be used to discriminate tumor cells from benign hepatic cells.

Figure 1

Serum α-fetoprotein levels in 107 patients with liver cirrhosis or hepatocellular carcinoma at late Barcelona Clinic Liver Cancer stages (A) and early Barcelona Clinic Liver Cancer stages (B). Each dot represents one patient. AFP: α-fetoprotein; HCC: Hepatocellular carcinoma; BCLC: Barcelona Clinic Liver Cancer.

Figure 2

Serum glypican-3 levels in 32 liver cirrhosis patients and in 37 hepatocellular carcinoma patients at Barcelona Clinic Liver Cancer-stage A and B. A: Each dot represents one patient; B: Frequencies of α-fetoprotein (AFP) ≥ 400 μg/L and glypican-3 (GPC3) > 300 ng/L in hepatocellular carcinoma (HCC) patients at Barcelona Clinic Liver Cancer-stage A and B.

Figure 3

Immunohistochemistry staining of glypican-3 or α-fetoprotein in liver samples. Representative of the excised hepatocellular carcinoma samples stained with mouse anti-glypican-3 (GPC3) (A-C) or AFP (D, 4 ×); B (10 ×) and c (40 ×) are the amplified image of A (4 ×). The cells stained with yellow or brown particles were considered positive (arrows).

Figure 4

Immunohistochemistry staining of glypican-3 in needle biopsy. Three tissue sections (A-C, 10 ×) from patients with hepatic space occupying lesions with their serum α-fetoprotein < 400 μg/L. Glypican-3 was positively expressed in hepatocellular carcinoma (arrows).

Figure 5

Frequencies of serum α-fetoprotein ≥ 400 μg/L only (stripped bars), α-fetoprotein ≥ 400 μg/L and glypican-3 > 300 ng/L (filled bars) in 75 hepatocellular carcinoma patients at different Barcelona Clinic Liver Cancer stages. AFP: α-fetoprotein; GPC3: Glypican-3.