Merlo Andrea, Casalini Patrizia, Carcangiu Maria Luisa, Malventano Chiara, Triulzi Tiziana, Mènard Sylvie, Tagliabue Elda, Balsari Andrea
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.
J Clin Oncol. 2009 Apr 10;27(11):1746-52. doi: 10.1200/JCO.2008.17.9036. Epub 2009 Mar 2.
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.
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.
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%).
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.
转录因子叉头框P3（FOXP3）可上调或下调大量基因，最近有报道称其在肿瘤细胞中表达。我们研究了FOXP3表达在乳腺癌患者中的预后重要性。
采用免疫组织化学方法对米兰3期和1期试验患者的原发性乳腺癌标本中FOXP3的表达模式进行了表征。根据FOXP3表达的有无，使用Kaplan-Meier分析和Cox比例风险回归模型来评估总生存期、无远处转移生存期和局部复发累积发生率。
肿瘤中FOXP3的表达与较差的总生存概率相关，且风险随FOXP3免疫染色强度的增加而增加。FOXP3也是无远处转移生存期的一个强有力的预后因素，但不是局部复发风险的预后因素。在多变量分析中，FOXP3是一个独立的预后因素，FOXP3表达和淋巴结阳性的风险比相似。在米兰3期试验中，淋巴结阴性亚组中FOXP3阴性患者的10年生存率为100%，FOXP3阳性患者为82%；淋巴结阳性亚组中FOXP3阴性患者为82%，FOXP3阳性患者为41%。即使在米兰1期试验中，淋巴结阳性亚组中FOXP3表达缺失与比FOXP3阳性患者显著更好的预后相关（10年生存率，89%对59%）。
这些数据确定FOXP3表达是乳腺癌中的一个新的独立预后因素，这可能有助于改善患者的适当治疗选择。
