FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes is associated with breast cancer prognosis.
FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes is associated with breast cancer prognosis.
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DOI：
10.3892/mco.2013.107
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发表时间：
2013-07
影响因子：
1.2
通讯作者：
Kage M
中科院分区：
文献类型：
--
作者：
Takenaka M;Seki N;Toh U;Hattori S;Kawahara A;Yamaguchi T;Koura K;Takahashi R;Otsuka H;Takahashi H;Iwakuma N;Nakagawa S;Fujii T;Sasada T;Yamaguchi R;Yano H;Shirouzu K;Kage M
叉头盒蛋白 3 (FOXP3) 转录因子在肿瘤细胞和调节性 T 细胞 (Treg) 中高度表达。它在 Tregs 中发挥肿瘤增强作用，并作为多种癌基因的有效抑制因子抑制癌发生。 FOXP3表达的临床预后价值尚未阐明。本研究采用免疫组织化学方法探讨乳腺癌患者肿瘤细胞和肿瘤浸润淋巴细胞（TIL）中 FOXP3 表达的预后意义。在从原发性浸润性乳腺癌获得的 100 个肿瘤标本中，分别有 63% 和 57% 被评估为 FOXP3+ 肿瘤细胞和被 FOXP3+ 淋巴细胞高度浸润。尽管肿瘤细胞中 FOXP3 的表达没有预后意义，但 FOXP3+ 淋巴细胞与较差的总生存期 (OS) 显着相关（n=98，对数秩检验 P=0.008）。 FOXP3 在肿瘤细胞中表现出异质性亚细胞定位（细胞质，31%；细胞核，26%；两者，6%），尽管细胞质 FOXP3 与 OS 较差相关（P = 0.058），但细胞核 FOXP3 与 OS 改善显着相关（P = 0.016）。此外，当根据肿瘤细胞质 FOXP3 和淋巴细胞 FOXP3 的表达对患者进行分组时，OS 的 Kaplan-Meier 曲线存在显着差异 (P<0.001)，其中 FOXP3+ 淋巴细胞的高浸润伴随细胞质 FOXP3+ 肿瘤是最有害的表型。这些发现表明淋巴细胞和肿瘤细胞中的 FOXP3 表达可能是乳腺癌的预后标志物。根据其定位，肿瘤细胞中的 FOXP3 可能具有不同的生物学活性和预后价值，这可能有助于建立适当的癌症治疗方法。
The forkhead box protein 3 (FOXP3) transcription factor is highly expressed in tumor cells as well as in regulatory T cells (Tregs). It plays a tumor-enhancing role in Tregs and suppresses carcinogenesis as a potent repressor of several oncogenes. The clinical prognostic value of FOXP3 expression has not yet been elucidated. In this study, immunohistochemistry was used to investigate the prognostic significance of FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes (TILs) in breast cancer patients. Of the 100 tumor specimens obtained from primary invasive breast carcinoma, 63 and 57% were evaluated as FOXP3+ tumor cells and as being highly infiltrated by FOXP3+ lymphocytes, respectively. Although FOXP3 expression in tumor cells was of no prognostic significance, FOXP3+ lymphocytes were significantly associated with poor overall survival (OS) (n=98, log-rank test P=0.008). FOXP3 exhibited a heterogeneous subcellular localization in tumor cells (cytoplasm, 31%; nucleus, 26%; both, 6%) and, although cytoplasmic FOXP3 was associated with poor OS (P= 0.058), nuclear FOXP3 demonstrated a significant association with improved OS (P=0.016). Furthermore, when patients were grouped according to their expression of tumor cytoplasmic FOXP3 and lymphocyte FOXP3, there were notable differences in the Kaplan-Meier curves for OS (P<0.001), with a high infiltration of FOXP3+ lymphocytes accompanied by a cytoplasmic FOXP3+ tumor being the most detrimental phenotype. These findings indicated that FOXP3 expression in lymphocytes as well as in tumor cells may be a prognostic marker for breast cancer. FOXP3 in tumor cells may have distinct biological activities and prognostic values according to its localization, which may help establish appropriate cancer treatments.