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. 2013 Sep;13(3):703-9.
doi: 10.4314/ahs.v13i3.26.

Diagnostic value of glypican-3 in alpha fetoprotein negative hepatocellular carcinoma patients

B Li  1 , H Liu, H W Shang, P Li, N Li, H G Ding
Affiliations

Diagnostic value of glypican-3 in alpha fetoprotein negative hepatocellular carcinoma patients

B Li et al. Afr Health Sci. 2013 Sep.

Abstract

Background: The prognosis of patients with hepatocellular carcinoma(HCC) is generally very poor with a 5-year survival rate of less than 15% since most of them are diagnosed clinically at their late stage. However, the differential diagnosis between alpha fetoprotein(AFP) negative HCC and cirrhotic nodules is still difficult.

Objectives: To evaluate the diagnostic value of glypican-3(GPC3) in patients with AFP negative hepatitis B related HCC.

Methods: The liver tissue GPC3 (GPC3L) expression was tested from 426 for surgery and 179 of needle biopsies of hepatitis B related HCC patients using immunohistochemistry staining. Serum GPC3 (GPC3S) and AFP were also measured.

Results: Among surgical HCC samples, 80.0% of GPC3L expression was positive, however, in paracarcinomatous and cirrhotic nodules were negative. In needle biopsy tissues, GPC3L positively expression was in 74.9%. The sensitivity of AFP>400 µg/L was 25.4%. The GPC3S >3.5 µg/L was determined as a positive. The area of ROC curve of GPC3S was 0.68(95% CI 0.56-0.79,P<0.05) in all HCC patients,0.81 (95% CI 0.62 -0. 98, P<0.05) in AFP greater or equal to 400 µg/L and 0.64 (95% CI 0.51-0.77, P=0.051) in AFP negative patients. The GPC3S was positive in 48.8% of patients with AFP negative. No difference was observed between GPC3L/GPC3S and serum AFP.

Conclusions: GPC3 may be helpful in improving diagnosis of HCC and in differentiating diagnosis between AFP negative HCC and cirrhotic nodules.

Keywords: Alpha fetoprotein; Differential diagnosis; Glypican-3; Hepatitis B; Hepatocellular carcinoma.

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Figures

Figure 1
Figure 1
IHC staining of GPC3 in HCC liver samples A-C (10x). The cells stained with brown particles were considered as positive (arrow). A: The area of cirrhosis liver around the HCC has no GPC3 expression. B: There was no labeling in area with non-cirrhosis liver around the HCC. C: The area of portal venous tumor thrombus showed strong GPC3 expression(arrow).
Figure 2 A–B
Figure 2 A–B
The relationship between GPC3L/GPC3S with serum AFP
Figure 3
Figure 3
The diagnostic accuracy of GPC3S was performed by ROC curves. The GPC3S was over 3.5µg/L in 48.8% of patients with AFP<400µg/L. The sensitivity and specificity in all, AFP greater or equal to 400µg/L and AFP negative HCC patients were 54.6%, 75%, 54.6% and 80%, 80%, 76%, respectively. The positive predictive value and negative predictive value were 83.3%, 60%, 77.8% and 43.2%, 86.4%, 46.3%, respectively
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