Correlation of CXCL12/CXCR4 Expression and FOXP3 Cell Infiltration in Normal Endometrium, Typical and Atypical Hyperplasia and Endometrioid Adenocarcinoma
Neera Maroo, Roberto E Dina. Hammersmith Hospital, Imperial College London, London, United Kingdom
Background: Chemokines and chemokine receptors are also known to play a role in both immunity and the inhibition or growth of cancer cells. Recent studies on human cervical and ovarian cancer have shown there to be an overproduction of the chemokine CXCL12 and its receptor (CXCR4) which is now known to be related to cancer progression.
Design: AIM: to investigate whether a correlation between CXCL12/CXCR4 expression and FoxP3+ Treg cell infiltration in normal endometrium (NORMAL), simple hyperplasia (SH), complex non-atypical/ typical (CTH), complex atypical hyperplasia (CAH) and endometrioid adenocarcinoma (EA) exists.
METHODOLOGY: Our study consisted of building a progressive TMA with:17 NORMAL patient cases,20 SH + CTH patient cases,16 CAH patient cases and 40 EA patient cases.This investigation compared a total of 93 patient cases from the extraction of 259 tissue cores which were subjected to IHC staining. Slides were scored via light miscopy to measure the percentage of positive Foxp3 T- cells and the percentage area x intensity of CXCL12/CXCR4 expression.
Results: One-way analysis of variance (ANOVA) was followed by post hoc analysis using Tukey's Multiple Comparison Test which revealed statistically significant differences between the amount of CXCL12 expression, CXCR4 expression and Foxp3 T cell infiltration between Normal, SH + CTH, CAH and EA patient groups (P < 0.001).
As for FoxP3 Treg infiltration post hoc analysis by Tukey's Multiple Comparison Test identified: Normal vs SH + CTH (q = 5.26, P< 0.05), Normal vs CAH (q = 8.853, P< 0.05), Normal vs EA (q = 6.735, P< 0.05), SH + CTH vs CAH (q = 4.043, P< 0.05) and CAH vs EA (q = 3.929, P< 0.05) to have statistically significant differences, with the exception of: SH + CTH vs EA groups which showed no statistically significant difference (q= 0.74, P >0.05).
Conclusions: We observed increasing CXCL12 and CXCR4 expression which correlated with increasing endometrial per-neoplastic changes and cancer. Trends for Foxp3 Treg infiltration showed to increase with increasing prE-neoplastic morphology, however unexpectedly higher Foxp3 levels were seen in CAH when compared to EA patients. Despite these differences, a weak positive correlation was observed between increasing Foxp3 Treg infiltration and increasing CXCL12 expression (Spearman correlation, P value <0.004**, 2 tailed test, r = 0.30), indicating potential chemoattractant properties of CXCL12 regarding Tregs.
Category: Gynecologic & Obstetrics
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 133, Tuesday Afternoon