Prognostic impact of FOXP3 expression in triple-negative breast cancer.
BACKGROUND
Forkhead Box Protein 3 (FOXP3) is a marker for immunosuppressive CD4+CD25+ regulatory T cells (Tregs). We investigated whether there were significant numbers of FOXP3-positive Tregs in triple-negative breast cancer (TNBC) using immunohistochemistry, and whether the presence of FOXP3-positive Tregs was associated with other prognostic factors, such as stage or histologic grade. We investigated the number of tumor-infiltrating FOXP3-positive Tregs in formalin-fixed TNBC specimens obtained from patients who received palliative treatment between 1999 and 2007.


METHODS
Immunohistochemistry was used to assess the number of CD4+, CD25+, and FOXP3+ Tregs in tumor tissue and normal breast tissue from 86 TNBC patients. Univariate and multivariate analyses evaluated outcomes according to the number of FOXP3-positive Tregs.


RESULTS
Of the 86 tumor specimens, 22 (25.6%) expressed more than 15 FOXP3-positive Tregs per 10 high power fields in the peritumoral area. On multivariate analysis, staining showing ≥ 15 FOXP3-positive Tregs was an independent prognostic factor for overall survival and progression free survival with hazard ratios of 2.4 (95% CI 1.0-5.6; p = 0.049) and 2.0 (95% CI 1.1-3.6; p = 0.032), respectively. In TNBC, FOXP3-positive Tregs had stronger prognostic significance than did FOXP3-negative Tregs. The finding of improved survival associated with highly infiltrating FOXP3-positive Tregs in TNBC contrasted with several other types of solid cancer.


CONCLUSIONS
TNBC may be differently driven by FOXP3 via an immune mechanism. The inclusion of FOXP3+ Tregs may help to improve prognostication for TNBC.
Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.
Soohyeon
S
Lee
Eun Yoon
EY
Cho
Yeon Hee
YH
Park
Jin Seok
JS
Ahn
Young-Hyuck
YH
Im
D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018572:Disease-Free Survival; D004363:Drug Utilization; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008207:Lymphatic Metastasis; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D010997:Pleural Neoplasms / Q000556:secondary; D011379:Prognosis; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D043823:Taxoids / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D043823:Taxoids; C080625:taxane