Prognostic value of tumor-infiltrating FOXP3+ regulatory T cells in patients with hepatocellular carcinoma

A. Sasaki, F. Tanaka, Koshi Mimori, H. Inoue, S. Kai, K. Shibata, M. Ohta, S. Kitano, Masaki Mori

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Abstract

Aims: CD4+ CD25+ forkhead box P3 (FOXP3)+ Treg accumulate in malignant tumors and negatively regulate anti-tumor immunity. To determine the prognostic value of tumor-infiltrating regulatory T cells (Treg), 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+ Treg in formalin-fixed HCC specimens. The number of FOXP3+ Treg 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+ Treg was accessed by univariate and multivariate analyses. Results: The mean and median numbers of tumor-infiltrating Treg were 29.0 and 14 per 10 HPF for FOXP3+ Treg. The number of FOXP3+ Treg was positively correlated with preoperative serum alpha-fetoprotein levels. The disease-free survival rate was significantly lower in patients with high Treg counts (≥14, n = 84) than in those with low Treg counts (<14, n = 80) (13.6% vs. 25.7% at 5 years; P = 0.02). By multivariate analysis, the high Treg 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 Treg is an independent predictive factor of tumor recurrence after hepatic resection for HCC.

Original languageEnglish
Pages (from-to)173-179
Number of pages7
JournalEuropean Journal of Surgical Oncology
Volume34
Issue number2
DOIs
Publication statusPublished - Feb 1 2008

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Regulatory T-Lymphocytes
Hepatocellular Carcinoma
Neoplasms
Multivariate Analysis
Survival Rate
Recurrence
Liver
alpha-Fetoproteins
Aspartate Aminotransferases
Portal Vein
Formaldehyde
Disease-Free Survival
Microscopy
Immunity
Retrospective Studies
Cell Count
Light
Serum

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

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Prognostic value of tumor-infiltrating FOXP3+ regulatory T cells in patients with hepatocellular carcinoma. / Sasaki, A.; Tanaka, F.; Mimori, Koshi; Inoue, H.; Kai, S.; Shibata, K.; Ohta, M.; Kitano, S.; Mori, Masaki.

In: European Journal of Surgical Oncology, Vol. 34, No. 2, 01.02.2008, p. 173-179.

Research output: Contribution to journalArticle

Sasaki, A. ; Tanaka, F. ; Mimori, Koshi ; Inoue, H. ; Kai, S. ; Shibata, K. ; Ohta, M. ; Kitano, S. ; Mori, Masaki. / Prognostic value of tumor-infiltrating FOXP3+ regulatory T cells in patients with hepatocellular carcinoma. In: European Journal of Surgical Oncology. 2008 ; Vol. 34, No. 2. pp. 173-179.
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abstract = "Aims: CD4+ CD25+ forkhead box P3 (FOXP3)+ Treg accumulate in malignant tumors and negatively regulate anti-tumor immunity. To determine the prognostic value of tumor-infiltrating regulatory T cells (Treg), 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+ Treg in formalin-fixed HCC specimens. The number of FOXP3+ Treg 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+ Treg was accessed by univariate and multivariate analyses. Results: The mean and median numbers of tumor-infiltrating Treg were 29.0 and 14 per 10 HPF for FOXP3+ Treg. The number of FOXP3+ Treg was positively correlated with preoperative serum alpha-fetoprotein levels. The disease-free survival rate was significantly lower in patients with high Treg counts (≥14, n = 84) than in those with low Treg counts (<14, n = 80) (13.6{\%} vs. 25.7{\%} at 5 years; P = 0.02). By multivariate analysis, the high Treg 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 Treg is an independent predictive factor of tumor recurrence after hepatic resection for HCC.",
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AU - Mimori, Koshi

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AU - Kai, S.

AU - Shibata, K.

AU - Ohta, M.

AU - Kitano, S.

AU - Mori, Masaki

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N2 - Aims: CD4+ CD25+ forkhead box P3 (FOXP3)+ Treg accumulate in malignant tumors and negatively regulate anti-tumor immunity. To determine the prognostic value of tumor-infiltrating regulatory T cells (Treg), 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+ Treg in formalin-fixed HCC specimens. The number of FOXP3+ Treg 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+ Treg was accessed by univariate and multivariate analyses. Results: The mean and median numbers of tumor-infiltrating Treg were 29.0 and 14 per 10 HPF for FOXP3+ Treg. The number of FOXP3+ Treg was positively correlated with preoperative serum alpha-fetoprotein levels. The disease-free survival rate was significantly lower in patients with high Treg counts (≥14, n = 84) than in those with low Treg counts (<14, n = 80) (13.6% vs. 25.7% at 5 years; P = 0.02). By multivariate analysis, the high Treg 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 Treg is an independent predictive factor of tumor recurrence after hepatic resection for HCC.

AB - Aims: CD4+ CD25+ forkhead box P3 (FOXP3)+ Treg accumulate in malignant tumors and negatively regulate anti-tumor immunity. To determine the prognostic value of tumor-infiltrating regulatory T cells (Treg), 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+ Treg in formalin-fixed HCC specimens. The number of FOXP3+ Treg 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+ Treg was accessed by univariate and multivariate analyses. Results: The mean and median numbers of tumor-infiltrating Treg were 29.0 and 14 per 10 HPF for FOXP3+ Treg. The number of FOXP3+ Treg was positively correlated with preoperative serum alpha-fetoprotein levels. The disease-free survival rate was significantly lower in patients with high Treg counts (≥14, n = 84) than in those with low Treg counts (<14, n = 80) (13.6% vs. 25.7% at 5 years; P = 0.02). By multivariate analysis, the high Treg 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 Treg is an independent predictive factor of tumor recurrence after hepatic resection for HCC.

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