title: Akt phosphorylation is a risk factor for early disease recurrence and poor prognosis in hepatocellular carcinoma.
abstract: BACKGROUND
  Patients with hepatocellular carcinoma (HCC) who showed early massive disease recurrence due to hematogenous intrahepatic metastasis after curative resection had a poor prognosis. The authors previously reported that Akt phosphorylation was correlated with hematogenous intrahepatic metastasis, using HCC cell lines.
  
  
  METHODS
  The authors analyzed clinicopathologic features and the status of selected biologic markers, including phosphorylated Akt, to identify risk factors for early disease recurrence and poor prognosis in HCC. In the current series, 49 postoperative patients developed intrahepatic disease recurrence within 6 months (Group 1) and 86 patients remained disease recurrence free > 3 years after resection (Group 2). Group 1 was further divided into 2 subgroups: 19 patients who died of disease recurrence within a year after resection (Group 1A) and 27 patients who survived > 1 year (Group 1B).
  
  
  RESULTS
  Using univariate analysis, the risk factors for early disease recurrence were tumor size, macroscopic classification, tumor differentiation, microscopic capsule infiltration, microscopic portal vein (MPV) invasion, microscopic intrahepatic metastasis (MIM), and positive immunostaining for phosphorylated Akt, Ki-67, and p53 (P < 0.05). The risk factors for poor prognosis were the number of intrahepatic metastases, tumor differentiation, and positive immunostaining for phosphorylated Akt and Ki-67 (P < 0.05). Multivariate analysis revealed that the risk factors for early disease recurrence were MPV invasion, MIM, and positive immunostaining for phosphorylated Akt, and that the risk factors for poor prognosis were positive immunostaining for phosphorylated Akt and Ki-67 (P < 0.05).
  
  
  CONCLUSIONS
  The current clinical study showed the critical involvement of Akt phosphorylation in the aggressiveness of HCC. The potential benefits of surgery should be assessed carefully in patients with any of these risk factors.
authors.affiliation: Division of Pathology, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Michiie
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Susumu
authors.initials: S
authors.lastname: Yamasaki
authors.forename: Satoru
authors.initials: S
authors.lastname: Todo
authors.forename: Setsuo
authors.initials: S
authors.lastname: Hirohashi
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D016009:Chi-Square Distribution; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006498:Hepatectomy; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D010766:Phosphorylation; D011336:Probability; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D011518:Proto-Oncogene Proteins; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt