Prognostic value of tumor-infiltrating FOXP3+ regulatory T cells in patients with hepatocellular carcinoma.
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.
Sasaki
A
A
Department of Surgery, National Hospital Organization Miyazaki Hospital, 19403-4 Kawaminami-machi, Miyazaki 889-1301, Japan.
Tanaka
F
F
Mimori
K
K
Inoue
H
H
Kai
S
S
Shibata
K
K
Ohta
M
M
Kitano
S
S
Mori
M
M
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*
D014408:Biomarkers, Tumor; D051543:Hepatocyte Nuclear Factor 3-gamma