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

ObjectivesCD4+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.MethodsParaffin-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-1α and HIF-2α, VEGF, estrogen and progesterone receptor expression. Survival analysis was also performed.ResultsIn normal endometrium, FOXP3 was expressed by stroma infiltrating lymphocytes, with a mean number 8 (range 5–11) lymphocytes per ×100 optical field. In tumors, 55/79 (69.6%) cases showed little FOXP3+ lymphocytic infiltration (0–2 per ×100 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.ConclusionsThe 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.