title: Prognostic value of tumor-infiltrating FOXP3+ regulatory T cells in patients with hepatocellular carcinoma.
abstract: OBJECTIVE
  CD4+ CD25+ forkhead box P3 (FOXP3)+ T(reg) accumulate in malignant tumors and negatively regulate anti-tumor immunity. To determine the prognostic value of tumor-infiltrating regulatory T cells (T(reg)), we conducted a retrospective study on 164 patients with hepatocellular carcinoma (HCC) who underwent curative hepatic resection.
  
  
  METHODS
  We investigated the number of tumor-infiltrating FOXP3+ T(reg) in formalin-fixed HCC specimens. The number of FOXP3+ T(reg) for each case was calculated as the total number of positive cells per 10 high-power fields (HPF) on light microscopy. Long-term survival rate after resection according to the number of FOXP3+ T(reg) was accessed by univariate and multivariate analyses.
  
  
  RESULTS
  The mean and median numbers of tumor-infiltrating T(reg) were 29.0 and 14 per 10 HPF for FOXP3+ T(reg). The number of FOXP3+ T(reg) was positively correlated with preoperative serum alpha-fetoprotein levels. The disease-free survival rate was significantly lower in patients with high T(reg) counts (> or =14, n=84) than in those with low T(reg) counts (<14, n=80) (13.6% vs. 25.7% at 5 years; P=0.02). By multivariate analysis, the high T(reg) counts, presence of portal vein invasion, and elevation of preoperative aspartate aminotransferase level were independent predictive factors of tumor recurrence.
  
  
  CONCLUSIONS
  The high number of tumor-infiltrating T(reg) is an independent predictive factor of tumor recurrence after hepatic resection for HCC.
authors.affiliation: Department of Surgery, National Hospital Organization Miyazaki Hospital, 19403-4 Kawaminami-machi, Miyazaki 889-1301, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Sasaki
authors.forename: F
authors.initials: F
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Mimori
authors.forename: H
authors.initials: H
authors.lastname: Inoue
authors.forename: S
authors.initials: S
authors.lastname: Kai
authors.forename: K
authors.initials: K
authors.lastname: Shibata
authors.forename: M
authors.initials: M
authors.lastname: Ohta
authors.forename: S
authors.initials: S
authors.lastname: Kitano
authors.forename: M
authors.initials: M
authors.lastname: Mori
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D015331:Cohort Studies; D016001:Confidence Intervals; D018572:Disease-Free Survival; D005260:Female; D006498:Hepatectomy / Q000379:methods; D051543:Hepatocyte Nuclear Factor 3-gamma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011336:Probability; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D051543:Hepatocyte Nuclear Factor 3-gamma