title: Prognostic significance of glutamine synthetase expression in unifocal advanced hepatocellular carcinoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgical Oncology, Graduate School of Medicine, University of Tokyo, Japan. OSADA-1SU@h.u-tokyo.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Osada
authors.forename: I
authors.initials: I
authors.lastname: Nagashima
authors.forename: N H
authors.initials: NH
authors.lastname: Tsuno
authors.forename: J
authors.initials: J
authors.lastname: Kitayama
authors.forename: H
authors.initials: H
authors.lastname: Nagawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000096:biosynthesis*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D005974:Glutamate-Ammonia Ligase