Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.
Acta Oncol. 2013 Jan;52(1):73-81. doi: 10.3109/0284186X.2012.731520. Epub 2012 Oct 17.
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.
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.
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.
TNBC may be differently driven by FOXP3 via an immune mechanism. The inclusion of FOXP3+ Tregs may help to improve prognostication for TNBC.
叉头框蛋白 3（FOXP3）是免疫抑制性 CD4+CD25+调节性 T 细胞（Tregs）的标志物。我们通过免疫组织化学方法研究了三阴性乳腺癌（TNBC）中是否存在大量 FOXP3+Tregs，以及 FOXP3+Tregs 的存在是否与其他预后因素（如分期或组织学分级）相关。我们研究了 86 例 TNBC 患者在 1999 年至 2007 年期间接受姑息治疗时获得的福尔马林固定 TNBC 标本中肿瘤浸润性 FOXP3+Tregs 的数量。
免疫组织化学用于评估 86 例 TNBC 患者肿瘤组织和正常乳腺组织中 CD4+、CD25+和 FOXP3+Tregs 的数量。单变量和多变量分析根据 FOXP3+Tregs 的数量评估结果。
在 86 个肿瘤标本中，22 个（25.6%）在肿瘤周围区域每 10 个高倍视野中表达超过 15 个 FOXP3+Tregs。多变量分析显示，染色显示≥15 个 FOXP3+Tregs 是总生存和无进展生存的独立预后因素，风险比分别为 2.4（95%CI 1.0-5.6；p=0.049）和 2.0（95%CI 1.1-3.6；p=0.032）。在 TNBC 中，FOXP3+Tregs 的预后意义强于 FOXP3-Tregs。与其他几种实体瘤相比，在 TNBC 中，FOXP3 阳性 Tregs 浸润程度较高与生存改善相关。
FOXP3 可能通过免疫机制以不同的方式驱动 TNBC。FOXP3+Tregs 的纳入可能有助于改善 TNBC 的预后。
