Regulatory T-Cells in Breast Cancer Sentinel Nodes: FOXP3 Expression Analysis.
Payal M Sojitra, Mangesh Thorat, Rohit K Jain, Rutika Mehta, Sunil Badve. Indiana University School of Medicine, Indianapolis
Background: Host immune response play an important role in breast cancer. Primary breast tumors with predominant Th-1 response have better survival. Tumors with higher proportions of T-regs including Th-1 to Th-2 shift have poor outcome. FOXP3 (forkhead box P3) is a member of forkhead / winged helix family of transcriptional regulators and functions as the master regulator in the development and function of T-regs. FOXP3 is also a good immunohistochemistry (IHC) marker for identifying T-regs. It is generally accepted that recruitment of T-regs in tumor may help cancer cells to evade host immune responses. However host immune responses after cancer cells have escaped primary tumor is not well established. This study analyzes FOXP3 expression in sentinel nodes (SN) with and without metastatic breast cancer.
Design: SNs with metastasis (n= 68) or without metastasis (N=70) were randomly selected and analyzed for expression of FOXP3 by IHC using FOXP3 antibody 236/E7 (Abcam). Cortical cells expressing FOXP3 (nuclear expression) were counted in 10 high power fields. Results of estrogen (ER),progesterone (PR) and HER2 receptor status of the primary tumors were available for these patients. Data were analyzed using SPSS 18.0 software.
Results: SN positive and SN negative groups were well balanced for all clinico-pathological parameters. FOXP3 expression was evaluable in 66 SN positive and 69 SN negative;3 cases were lost during IHC staining. The mean number of FOXP3 positive cells in SN positive cases and SN negative cases did not differ significantly (mean 139 and 132 respectively; p=0.540). Younger patients (age <35) had higher FOXP3 expression (mean 162) as compared to older patients (mean =133; p=0.250) but did not reach statistical significance. FOXP3 expression did not differ significantly between 2 groups even after adjusting for age. FOXP3 expression also did not correlate with molecular subtypes of breast cancer based on IHC (Neilsen et al) definition.
Conclusions: T-regs recruitment is not altered after regional metastasis indicating evasion of local immune mechanism(s). This may be one reason why secondary immunological approaches (e.g. antibody therapies) rather than primary approaches (e.g. vaccines) have been more successful in breast cancer with evidence of nodal or systemic metastasis.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 13, Wednesday Afternoon