The presence of tumor-infiltrating FOXP3+ lymphocytes correlates with intratumoral angiogenesis in endometrial cancer.
OBJECTIVE
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.
Giatromanolaki
Alexandra
A
Department of Pathology, Democritus University of Thrace, Alexandroupolis 68100, Greece. targ@her.forthnet.gr
Bates
Gaynor J
GJ
Koukourakis
Michael I
MI
Sivridis
Efthimios
E
Gatter
Kevin C
KC
Harris
Adrian L
AL
Banham
Alison H
AH
D000230:Adenocarcinoma / Q000097:blood / Q000098:blood supply* / Q000276:immunology* / Q000473:pathology; D016889:Endometrial Neoplasms / Q000097:blood / Q000098:blood supply* / Q000276:immunology* / Q000473:pathology; D004717:Endometrium / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000097:blood / Q000276:immunology / Q000473:pathology; D011960:Receptors, Estrogen / Q000096:biosynthesis; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D011960:Receptors, Estrogen