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.
Department of Pathology, Democritus University of Thrace, Alexandroupolis 68100, Greece. targ@her.forthnet.gr
Alexandra
A
Giatromanolaki
Gaynor J
GJ
Bates
Michael I
MI
Koukourakis
Efthimios
E
Sivridis
Kevin C
KC
Gatter
Adrian L
AL
Harris
Alison H
AH
Banham
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