Glypican-3 expression is correlated with poor prognosis in hepatocellular carcinoma

Abstract

The relationship between overexpression of glypican (GPC)-3 that is specific for hepatocellular carcinoma (HCC) and the prognosis has not yet been clarified. We attempted to determine the expression profile of GPC3 in association with the clinicopathological factors by immunohistochemical analysis in HCC patients and investigated the potential prognostic value of GPC3 by comparing the survival rate between the GPC3-positive and GPC3-negative HCC patients. Primary HCC tissue samples (n = 107) obtained from patients who had undergone hepatectomy between 2000 and 2001 were analyzed. GPC3 expression was less frequently observed in well-differentiated HCC than in moderately and poorly differentiated HCC, the difference in the frequency being statistically significant. GPC3-positive HCC patients had a significantly lower 5-year survival rate than the GPC3-negative HCC patients (54.5 vs 87.7%, P = 0.031). Among 80 of the 107 (74.6%) patients with initial treatment who underwent hepatectomy, none of GPC3-negative HCC patients (n = 16, 20.0%) died during the follow-up period. No deaths were noted in the GPC3-negative HCC patients among the 71 (88.7%) patients with moderately and poorly differentiated HCC. Multivariate analysis identified GPC3 expression (P = 0.034) as an independent prognostic factor for the overall survival. We showed that GPC3 expression is correlated with a poor prognosis in HCC patients.

Figure 1

Glypican (GPC)‐3 expression and localization is hepatocellular carcinoma (HCC)‐specific. (a,c) Microscopic view of a HE‐stained sections of resected HCC. (b,d) HCC sections were stained for GPC3 expression with anti‐GPC3 monoclonal antibody. (e) HCC displays prominent bile‐canalicular immunostaining. (f) Membranous and cytoplasmic staining of liver tumor cells are shown.

Figure 2

Overall survival curves for the 107 hepatocellular carcinoma (HCC) patients stratified into those with glypican (GPC)‐3‐positive and GPC3‐negative HCC. (a) Overall survival of patients with GPC3‐positive HCC was shorter than those with GPC3‐negative HCC (P = 0.031). (b) Overall survival curves in 80 of 107 HCC patients with initial treatment who underwent hepatectomy with positive and negative GPC3 expression. Patients with GPC3‐positive HCC had a lower 5‐year survival than those with GPC3‐negative HCC (P = 0.011). (c) Overall survival curves in the 71 HCC patients with initial hepatectomy who exhibited well‐ and moderately and poorly differentiated HCC on histopathological examination. The 5‐year survival rate was lower in the moderately and poorly differentiated GPC3‐positive HCC than in the corresponding GPC3‐negative HCC (P = 0.036). (d) Overall survival curves in the 71 initial treatment patients who underwent hepatectomy and exhibited moderately and poorly differentiated HCC on pathological examination with positive and negative GPC3 expression. The 5‐year survival rate was lower in the GPC3‐positive HCC patients than in the GPC3‐negative HCC patients (P = 0.035).