Tumor-Associated Macrophages as Potential Prognostic Biomarkers of Invasive Breast Cancer
Tumor-Associated Macrophages as Potential Prognostic Biomarkers of Invasive Breast Cancer
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DOI：
10.4048/jbc.2019.22.e5
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发表时间：
2019-03-01
影响因子：
2.4
通讯作者：
Kwon, Sun Young
中科院分区：
文献类型：
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作者：
Jeong, Hasong;Hwang, Ilseon;Kwon, Sun Young
目的：肿瘤相关巨噬细胞（TAM）是与各种癌症中的肿瘤进展相关的活化巨噬细胞。TAM可以是M1或M2类型。M1具有促炎功能并杀死病原体。相反，M2显示免疫抑制作用并促进肿瘤生长。TAM有多种标记。CD 11 c被认为是M1的特异性标志物。CD 163是M2的最佳标志物。CD 68被称为泛巨噬细胞标志物。我们评估了浸润性乳腺癌（IBC）的临床病理参数与CD 11 c、CD 163和CD 68的免疫组化表达之间的关系，以及肿瘤间质（TS）和肿瘤巢（TN）内巨噬细胞定位的预后价值。由2名病理学家对TN与TS中的CD 68+、CD 11 c+或CD 163+巨噬细胞数量进行计数。分析巨噬细胞（CD 68+、CD 11 c+、CD 163+）浸润程度与临床病理参数的相关性。我们还评估了巨噬细胞（CD 68+、CD 11 c+或CD 163+）对无病生存期（DFS）和总生存期（OS）的影响。结果：巨噬细胞（CD 68+、CD 11 c+或CD 163+）的高数量与较高的组织学分级、较高的Ki-67增殖指数、雌激素受体阴性和孕激素受体阴性相关。TS中大量巨噬细胞（CD 11 c+或CD 163+）与较大的肿瘤大小相关。此外，TN中的CD 163+巨噬细胞是OS和DFS降低的独立预后标志物。相反，TS中的CD 11 c+巨噬细胞是OS和DFS较高的独立预后标志物。结论：TAMs（包括M2型）与IBC中的肿瘤进展相关。它们也可以作为一个重要的不利或有利的预后因素。除了简单分析TAM的渗透程度外，分析TAM的位置也很重要。
Purpose: Tumor-associated macrophages (TAMs) are activated macrophages associated with tumor progression in various cancers. TAMs can polarize M1 or M2 type. M1 has a pro-inflammatory function and kills pathogens. Conversely, M2 shows immunosuppressive action and promotes tumor growth. There are various markers of TAMs. CD11c is considered as a specific marker of M1. CD163 is an optimal marker for M2. CD68 is known as a panmacrophage marker. We evaluated the relationship between the clinicopathological parameters and immunohistochemical expressions of CD11c, CD163, and CD68 in invasive breast cancer (IBC), and the prognostic value of macrophage localization within the tumor stroma (TS) and tumor nest (TN).Methods: Immunohistochemistry of CD68, CD11c, and CD163 was analyzed on tissue microarrays of 367 IBCs. The number of CD68+, CD11c+, or CD163+ macrophages in TN vs. TS was counted by 2 pathologists. The correlations between the degree of macrophage (CD68+, CD11c+, or CD163+) infiltration and the clinicopathological parameters were analyzed. We also assessed the impact of macrophages (CD68+, CD11c+, or CD163+) on disease free survival (DFS) and overall survival (OS).Results: High numbers of macrophages (CD68+, CD11c+, or CD163+) were associated with higher histologic grade, higher Ki-67 proliferating index, estrogen receptor negativity, and progesterone receptor negativity. High numbers of macrophages (CD11c+ or CD163+) in TS were associated with a larger tumor size. Furthermore, CD163+ macrophages in TN were an independent prognostic marker of reduced OS and DFS. Conversely, CD11c+ macrophages in TS were an independent prognostic marker for higher OS and DFS.Conclusion: TAMs, including M2 type, are associated with tumor progression in IBC. They can also act as a significant unfavorable or favorable prognostic factor. In addition to simply analyzing the degree of TAM infiltration, it is also important to analyze the location of TAMs.