Prognostic significance of glutamine synthetase expression in unifocal advanced hepatocellular carcinoma

Glutamine synthetase (GS) catalyzes the synthesis of glutamine, a major energy source of cells, and is upregulated in a subset of human hepatocellular carcinomas (HCCs). GS expression may be related to tumor recurrence, since GS-expressing tumors have a growth advantage in that they are independent of the extracellular glutamine supply. However, there are no studies concerning the prognostic value of GS expression in patients with HCC.

Seventy-three patients with a single advanced HCC nodule who underwent curative hepatectomy were included in the study. GS expression in the HCC nodules was analyzed immunohistochemically and was compared with clinicopathologic features and the behavior of the tumors. Survival curves were assessed according to the Kaplan-Meier product-limit method and multivariate analysis based on the Cox regression model was performed.

GS expression was strong in 26 cases (35.6%, high-GS group) and weak or absent in 47 cases (64.4%, low-GS group). Univariate analysis showed that the high-GS group had a significantly shorter disease-free survival time than the low-GS group (p=0.042). Multivariate analysis revealed that GS expression (p=0.021), as well as Child's classification (p=0.005) and portal invasion (p=0.039), was a significant and independent prognostic parameter that affected tumor recurrence.

The results of this study indicate that GS expression may enhance the metastatic potential in HCC, and GS immunostaining may be helpful in identifying HCC patients at high risk for disease recurrence.