Expression of M2-Polarized Macrophages is Associated with Poor Prognosis for Advanced Epithelial Ovarian Cancer
Expression of M2-Polarized Macrophages is Associated with Poor Prognosis for Advanced Epithelial Ovarian Cancer
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DOI：
10.7785/tcrt.2012.500312
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发表时间：
2013-06-01
影响因子：
2.8
通讯作者：
Liu, Jihong
中科院分区：
文献类型：
--
作者：
Lan, Chunyan;Huang, Xin;Liu, Jihong
在不同的微环境下，大细胞分化成两种功能不同的形式，M1和M2。肿瘤相关巨噬细胞（TAM）通常具有M2表型并促进肿瘤进展。迄今为止，很少有研究描述了卵巢癌中M2极化巨噬细胞的浸润。我们使用两种巨噬细胞标志物CD 68和CD 163来分析TAMs的表达，并阐明M2型与晚期卵巢癌生存率之间的关系。回顾性分析1999 - 2007年中山大学附属肿瘤防治中心收治的110例Ⅲ-Ⅳ期卵巢上皮性癌患者的临床资料。免疫组织化学染色CD 68和CD 163。分析巨噬细胞密度与患者存活率之间的相关性。我们的数据显示，在CD 68高表达组和低表达组患者之间的生存率没有显著差异。相比之下，低CD 163表达组的无进展生存期（PFS）率（p = 0.003）和总生存期（OS）率（p = 0.004）分别显著高于高CD 163表达组。同样，我们还观察到低CD 163/CD 68比值组患者的3年PFS（49.8% vs. 11.0%，p < 0.001）和OS（77.4% vs. 45.0%，p < 0.001）率显著高于高CD 163/CD 68比值组。多变量分析确定了CD 163阳性细胞密度以及CD 163/CD 68比值分别作为PFS和OS的阴性预测因子。我们的研究结果表明，CD 163阳性M2巨噬细胞的浸润以及M2表型巨噬细胞的活化可能导致晚期卵巢癌的生存率低。
Macrophages are polarized into two functionally distinct forms, M1 and M2, in response to different microenvironment. Tumor-associated macrophages (TAMs) generally have M2 phenotype and promote tumor progression. Few studies to date have described the infiltration of M2-polarized macrophages in ovarian cancer. We used two macrophages markers, CD68 and CD163, to analyze the expression of TAMs and to clarify the relationship between the M2 form and survival in advanced ovarian cancer. Clinical data of 110 patients with stages III-IV epithelial ovarian cancer at Sun Yat-sen University Cancer Center between 1999 and 2007 were retrospectively reviewed. Immunohistochemical staining of CD68 and CD163 was performed. Correlations between macrophage density and patient survival were analyzed. Our data showed that no significant difference was observed in survival between patients in the high- and the low-CD68 expression groups. In contrast, the progression-free survival (PFS) rates (p = 0.003) and overall survival (OS) rates (p = 0.004) were significantly higher in the low-CD163 expression group than in the high-CD163 expression group, respectively. Similarly, we also observed significantly improved 3-year PFS (49.8% vs. 11.0%, p < 0.001) and OS (77.4% vs. 45.0%, p < 0.001) rates in patients in the low-CD163/CD68 ratio group when compared with the high-CD163/CD68 ratio group. Multivariate analysis identified the density of CD163-positive cells as well as the ratio of CD163/CD68 as negative predictors for PFS and OS, respectively. Our results show that the infiltration of CD163-positive M2 macrophages as well as activation of macrophages towards the M2 phenotype may contribute to poor survival in advanced ovarian cancer.