FOXP3 expression and overall survival in breast cancer.
OBJECTIVE
The transcription factor forkhead box P3 (FOXP3) up- or downregulates a large number of genes and has been recently reported to be expressed in tumor cells. We investigated the prognostic importance of FOXP3 expression in patients with breast cancer.


METHODS
The expression patterns of FOXP3 were characterized by immunohistochemistry in primary breast carcinoma specimens from patients of the Milan 3 and 1 trials. Kaplan-Meier analysis and Cox proportional hazards regression modeling were used to assess the overall survival, distant metastasis-free survival, and local relapse cumulative incidence, according to the presence or absence of FOXP3 expression.


RESULTS
FOXP3 expression in tumors was associated with worse overall survival probability and the risk increased with increasing FOXP3 immunostaining intensity. FOXP3 was also a strong prognostic factor for distant metastases-free survival but not for local recurrence risk. In multivariate analysis FOXP3 resulted an independent prognostic factor and the hazard ratio of FOXP3 expression and of lymph node positivity were similar. In the Milan 3 trial, the probability of 10-year survival in node-negative subgroup was 100% for FOXP3-negative and 82% for FOXP3-positive patients; in node-positive subgroup 82% for FOXP3-negative and 41% for FOXP3-positive patients. Even in the Milan 1 trial the lack of FOXP3 expression in node-positive subgroup was related to a significantly better prognosis than in FOXP3-positive patients (10-year survival probability, 89% v 59%).


CONCLUSIONS
The data identify FOXP3 expression as a new independent prognostic factor in breast carcinoma, which might help to improve the selection of patients for appropriate therapy.
Merlo
Andrea
A
Molecular Biology Unit, Department of Experimental Oncology, Pathology Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori and the Institute of Pathology, University of Milan, Milan, Italy.
Casalini
Patrizia
P
Carcangiu
Maria Luisa
ML
Malventano
Chiara
C
Triulzi
Tiziana
T
Mènard
Sylvie
S
Tagliabue
Elda
E
Balsari
Andrea
A
D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors