Analysis of indoleamine 2-3 dioxygenase (IDO1) expression in breast cancer tissue by immunohistochemistry.
Analysis of indoleamine 2-3 dioxygenase (IDO1) expression in breast cancer tissue by immunohistochemistry.
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DOI：
10.1007/s00262-013-1393-y
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发表时间：
2013-05
期刊：
影响因子：
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通讯作者：
Ambs S
中科院分区：
文献类型：
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作者：
Soliman H;Rawal B;Fulp J;Lee JH;Lopez A;Bui MM;Khalil F;Antonia S;Yfantis HG;Lee DH;Dorsey TH;Ambs S
免疫抑制酶吲哚胺2，3双加氧酶（IDO）在许多不同的肿瘤类型（包括乳腺癌）中过表达。IDO抑制剂与化疗在乳腺癌小鼠模型中协同作用。表征乳腺癌中的IDO表达可以确定哪些患者接受IDO抑制剂。本研究分析了203例乳腺癌中IDO蛋白的表达。评估IDO、总生存期（OS）、疾病特异性生存期（DSS）、临床病理学、分子和免疫肿瘤浸润因素之间的关系。通过免疫组织化学评价IDO、雌激素受体（ER）、孕激素受体（PR）、人上皮受体2、细胞角蛋白5/6、上皮生长因子受体、磷酸化AKT、新血管生成、氮氧化物合成酶2（NOS 2）、环氧合酶2（COX 2）、FoxP 3、CD 8和CD 11b在存档乳腺癌组织切片上的表达。IDO和这些标志物之间的关联通过单变量和多变量分析进行了探讨。使用Kaplan-Meier（OS）和Wilcoxon双样本（DSS）检验分析生存率。与ER−肿瘤相比，ER+肿瘤中IDO表达更高。IDO在具有较高新血管生成的那些中较低。IDO高表达的ER+患者的OS更好。DSS在IDO高表达的淋巴结阳性患者中更好。IDO活性与NOS 2活性呈正相关。COX 2与IDO在单变量分析中呈正相关，但在多变量分析中无相关性。在IDO低的肿瘤中，CD 11b+细胞的数量有增加的趋势。IDO蛋白表达在ER乳腺肿瘤中较低，具有更大的新血管生成。未来评估IDO抑制剂和化疗之间协同作用的临床试验应考虑这一发现，并在试验设计中对ER状态进行分层。
The immunosuppressive enzyme, indoleamine 2,3 dioxygenase (IDO), is overexpressed in many different tumor types including breast cancer. IDO inhibitors synergize with chemotherapy in breast cancer murine models. Characterizing IDO expression in breast cancer could define which patients receive IDO inhibitors. This study analyzed IDO protein expression in 203 breast cancer cases. The relationship between IDO, overall survival (OS), disease-specific survival (DSS), clinicopathologic, molecular, and immune tumor infiltrate factors was evaluated. Expression of IDO, estrogen receptor (ER), progesterone receptor (PR), human epithelial receptor 2, cytokeratin 5/6, epithelial growth factor receptor, phosphorylated AKT, neoangiogenesis, nitrogen oxide synthetase 2 (NOS2), cyclooxygenase 2 (COX2), FoxP3, CD8, and CD11b on archival breast cancer tissue sections was evaluated by immunohistochemistry. Associations between IDO and these markers were explored by a univariate and multivariate analysis. Survival was analyzed using Kaplan–Meier (OS) and Wilcoxon two-sample (DSS) tests. IDO expression was higher in ER+ tumors compared to ER− tumors. IDO was lower in those with higher neoangiogenesis. OS was better in ER+ patients with high IDO expression. DSS was better in node-positive patients with high IDO expression. IDO activity positively correlates with NOS2. COX2 as positively correlated with IDO on univariate but not multivariate analysis. There was a trend toward greater numbers of CD11b+ cells in IDO-low tumors. IDO protein expression is lower in ER-breast tumors with greater neoangiogenesis. Future clinical trials evaluating the synergy between IDO inhibitors and chemotherapy should take this finding into account and stratify for ER status in the trial design.