Aikian Artem Z., Shynkevych Viktoriya I., Kaidashev Igor P
Ukrainian Medical Stomatological Academy, Poltava, Ukraine
Wiad Lek. 2019 Oct 31;72(10):1861-1865.
Introduction: Tumor-associated macrophages are an important prognostic factor and have been shown to be associated with invasion and migration of various types of cancer. Unlike M1-macrophages, which have pro-inflammatory and anti-cancer activity, M2-macrophages are immunosuppressive, promoting the restoration of the intracellular matrix, and therefore they contribute to the tumor growth. The aim: To study the quantitative characteristic and localization of CD68+ and CD163+ M2-like TAM that infiltrate non-luminal HER2-enriched carcinomas of BC in the primary focus without metastases and in paired specimens with metastases in the lymph nodes, as well as the pathomorphological characteristics of this type of BC.
The material of the study were intraoperative tissues of tumors and ipsilateral lymph nodes at radical removal of mammary glands. Immunohistochemical characteristics of the removed tumors (ER, PR, HER2, Ki67) were used to organize two groups of patients with primary BC according to the N1 / 0 status.
The statistical processing of the entire set of digital data confirmed a significant increase in CD68+TAM, but not CD163+M2 under metastatic conditions (p <0.0001), which may suggest an increase in M1-type TAM and their promotion of metastases in non-luminal HER2-enriched BC. Analysis of peculiarities of TAM localization showed that CD68+TAM was localized by clusters within the tumor nests and adjacent stroma, necrotized nests, whereas the typical localization of CD163+TAM M2-like macrophages predominated in the stroma and near the necrotic sites (where their quantitative characteristics coincide with those of CD68+TAM). This may indicate a relative predominance of M1 macrophages precisely in tumor nests. Along with the results on increased CD68+TAM (but not CD163+TAM) in metastases, it is possible to assume the contribution of M1 macrophages to the development / metastasis of BC, as prognosticated for other tumors.
A significant decrease in the number of CD68+TAM in metastases of the lymph node as compared with the primary clusters of BC, along with the absence of correlations, may reflect other functions of TAM in the affected lymph nodes or change of the tumor type in the metastasis.
肿瘤相关巨噬细胞是一个重要的预后因素，已被证明与各种类型癌症的侵袭和迁移有关。与具有促炎和抗癌活性的M1巨噬细胞不同，M2巨噬细胞具有免疫抑制作用，可促进细胞内基质的修复，因此它们有助于肿瘤生长。目的：研究浸润原发性无转移灶以及配对的有淋巴结转移的非腔面HER2富集型乳腺癌的CD68+和CD163+ M2样肿瘤相关巨噬细胞（TAM）的定量特征和定位，以及此类乳腺癌的病理形态学特征。
研究材料为乳腺根治术中肿瘤和同侧淋巴结的组织。根据N1/0状态，利用切除肿瘤的免疫组化特征（雌激素受体、孕激素受体、人表皮生长因子受体2、Ki67）将两组原发性乳腺癌患者进行分组。
对整套数字数据的统计处理证实，在发生转移的情况下，CD68+TAM显著增加，但CD163+M2没有增加（p<0.0001），这可能表明在非腔面HER2富集型乳腺癌中M1型TAM增加且它们促进了转移。对TAM定位特点的分析表明，CD68+TAM以簇状定位于肿瘤巢、相邻基质、坏死巢内，而CD163+TAM M2样巨噬细胞的典型定位主要在基质和坏死部位附近（其定量特征与CD68+TAM一致）。这可能表明恰恰在肿瘤巢中M1巨噬细胞相对占优势。结合转移灶中CD68+TAM（而非CD163+TAM）增加的结果，可以推测M1巨噬细胞对乳腺癌的发展/转移有作用，正如对其他肿瘤所预测的那样。
与乳腺癌的原发性簇相比，淋巴结转移灶中CD68+TAM数量显著减少，且不存在相关性，这可能反映了TAM在受累淋巴结中的其他功能或转移灶中肿瘤类型的变化。
