The presence of tumor-infiltrating FOXP3+ lymphocytes correlates with intratumoral angiogenesis in endometrial cancer

Gynecol Oncol. 2008 Aug;110(2):216-21. doi: 10.1016/j.ygyno.2008.04.021. Epub 2008 Jun 3.

Abstract

Objectives: CD4(+)CD25(+) regulatory T-cells (Tregs), that express the transcription factor FOXP3, suppress effector T-cell populations and can enable tumour cells to evade the host immune response. In this study, we investigated the numbers of FOXP3(+) Tregs in the normal and malignat endometrium and examined potential links with tumor angiogenesis.

Methods: Paraffin-embedded tissues from 79 patients with stage I endometrial adenocarcinoma and 12 samples from normal endometrium were analyzed using immunohistochemistry for the detection of FOXP3(+) lymphocytes. The presence of FOXP3(+) lymphocytic infiltration was correlated with the tumor vascular density, the hypoxia inducible factors HIF-1alpha and HIF-2alpha, VEGF, estrogen and progesterone receptor expression. Survival analysis was also performed.

Results: In normal endometrium, FOXP3 was expressed by stroma infiltrating lymphocytes, with a mean number 8 (range 5-11) lymphocytes per x100 optical field. In tumors, 55/79 (69.6%) cases showed little FOXP3(+) lymphocytic infiltration (0-2 per x100 optical field). In the remaining 24/79 (30.4%) cases that were scored as positive the mean score ranged from 3-8 (median 5). Low numbers of FOXP3(+) lymphocytes significantly correlated with tumoral ER negativity and low vascular density. Survival analysis showed no significant impact of FOXP3 lymphocytic infiltration, although there was a trend towards worse prognosis.

Conclusions: The correlation between the presence of FOXP3(+) Tregs and high vessel density in endometrial adenocarcinomas suggests a link between immunity, intratumoral angiogenesis and poor prognosis. However, further studies are required as significantly fewer Tregs were detected in the tumor microenvironment compared to normal endometrium.

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / blood supply*
  • Adenocarcinoma / immunology*
  • Adenocarcinoma / pathology
  • Endometrial Neoplasms / blood
  • Endometrial Neoplasms / blood supply*
  • Endometrial Neoplasms / immunology*
  • Endometrial Neoplasms / pathology
  • Endometrium / immunology
  • Female
  • Forkhead Transcription Factors / biosynthesis
  • Forkhead Transcription Factors / blood
  • Forkhead Transcription Factors / immunology*
  • Humans
  • Immunohistochemistry
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Neoplasm Staging
  • Neovascularization, Pathologic / blood
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Pathologic / pathology
  • Receptors, Estrogen / biosynthesis
  • Survival Rate
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Receptors, Estrogen