CD68+, but not stabilin-1+tumor associated macrophages in gaps of ductal tumor structures negatively correlate with the lymphatic metastasis in human breast cancer
CD68+, but not stabilin-1+tumor associated macrophages in gaps of ductal tumor structures negatively correlate with the lymphatic metastasis in human breast cancer
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DOI：
10.1016/j.imbio.2015.09.011
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发表时间：
2017-01-01
期刊：
影响因子：
2.8
通讯作者：
Kzhyshkowska, Julia
中科院分区：
文献类型：
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作者：
Buldakov, Mikhail;Zavyalova, Marina;Kzhyshkowska, Julia
肿瘤相关巨噬细胞（TAM）在几种乳腺癌动物模型中支持肿瘤生长和转移，并且TAM量预测有效的肿瘤生长和通过血液循环的转移扩散。然而，关于肿瘤内TAM异质性和TAM亚群在肿瘤进展中的功能作用的信息有限。本研究的目的是检测TAM在人乳腺癌不同形态学部位与临床参数的相关性。36例非特异性浸润性乳腺癌T1- 4 N 0 - 3 M0女性患者纳入本研究。使用Carl Zeiss Axio Lab. A1和MiraxMidiZeiss进行形态学检查。采用免疫组织化学和免疫荧光/共聚焦显微镜分析检测5个不同肿瘤节段中的CD 68和stabilin-1：（1）软纤维间质区域;（2）粗纤维间质区域;（3）最大间质和实质关系区域;（4）实质成分;（5）导管肿瘤结构间隙。CD 68在软纤维间质或间质-实质关系最密切的区域表达最高（79%）。CD 68在粗纤维间质区表达最低（23%）。发现肿瘤大小与管状肿瘤结构间隙中的CD 68表达呈负相关（R= -0.67; p= 0.02）。在淋巴结转移的情况下，导管间隙肿瘤结构中CD 68表达的平均评分（1.4 +/-0.5）低于阴性淋巴结情况（3.1 +/-1.0; F=10.9; p =0.007）。共聚焦显微镜鉴定了TAM的3种表型：CD 68 + stabilin-1-; CD 68 */stabilin-1（+）（超过50%）;和CD 68（-）/stabilin-1（+）。而stabilin-1的表达与淋巴结转移无关。我们得出结论，导管肿瘤结构间隙中CD 68 +TAM的量增加可保护区域淋巴结中的转移扩散。(C)2015作者由Elsevier GmbH出版。
Tumor associated macrophages (TAM) support tumor growth and metastasis in several animal models of breast cancer, and TAM amount is predictive for efficient tumor growth and metastatic spread via blood circulation. However, limited information is available about intratumoral TAM heterogeneity and functional role of TAM subpopulations in tumor progression. The aim of our study was to examine correlation of TAM presence in various morphological segments of human breast cancer with clinical parameters. Thirty six female patients with nonspecific invasive breast cancer T1-4N0-3M0 were included in the study. Morphological examination was performed using Carl Zeiss Axio Lab.A1 and MiraxMidiZeiss. Immunohistochemical and immunofluorescence/confocal microcopy analysis was used to detect CD68 and stabilin-1 in 5 different tumor segments: (1) areas with soft fibrous stroma; (2) areas with coarse fibrous stroma; (3) areas of maximum stromal-and-parenchymal relationship; (4) parenchymal elements; (5) gaps of ductal tumor structures. The highest expression of CD68 was in areas with soft fibrous stroma or areas of maximum stromal-and-parenchymal relationship (79%). The lowest expression of CD68 was in areas with coarse fiber stroma (23%). Inverse correlation of tumor size and expression of CD68 in gaps of tubular tumor structures was found (R= -0.67; p= 0.02). In case of the lymph node metastases the average score of CD68 expression in ductal gaps tumor structures was lower (1.4 +/- 0.5) compared to negative lymph nodes case (3.1 +/- 1.0; F=10.9; p =0.007). Confocal microscopy identified 3 phenotypes of TAM: CD68+istabilin-1-; CD68*/stabilin-1(+) (over 50%); and CD68(-)/stabilin-1(+). However, expression of stabilin-1 did not correlate with lymph node metastasis. We concluded, that increased amount of CD68+TAM in gaps of ductal tumor structures is protective against metastatic spread in regional lymph nodes. (C) 2015 The Authors. Published by Elsevier GmbH.