CD68+, but not stabilin-1+ tumor associated macrophages in gaps of ductal tumor structures negatively correlate with the lymphatic metastasis in human breast cancer

Autor: Vladimir Riabov, Julia Kzhyshkowska, Nadezhda V. Cherdyntseva, N. V. Krakhmal, Shuiping Yin, Irina Mitrofanova, Mikhail A. Buldakov, Bin Song, Nadezhda Telegina, M. V. Zavyalova, Sergei Vtorushin
Rok vydání: 2017
Předmět:
0301 basic medicine
Pathology
medicine.medical_specialty
Cell Adhesion Molecules
Neuronal

Stabilin-1
Immunology
Receptors
Lymphocyte Homing

Lymphatic metastasis
Antigens
Differentiation
Myelomonocytic

Gene Expression
Breast Neoplasms
Intratumoral heterogeneity
Metastasis
03 medical and health sciences
Breast cancer
0302 clinical medicine
Stroma
Antigens
CD

medicine
Humans
Immunology and Allergy
Neoplasm Metastasis
рак молочной железы
CD68
Lymph node
Aged
Neoplasm Staging
внутриопухолевая гетерогенность
business.industry
Macrophages
Tumor-associated macrophages
Carcinoma
Ductal
Breast

Cancer
Hematology
Middle Aged
medicine.disease
Immunohistochemistry
метастазы в лимфатических узлах
макрофаги
030104 developmental biology
medicine.anatomical_structure
Tumor progression
030220 oncology & carcinogenesis
Female
Lymph
business
Biomarkers
Zdroj: Immunobiology. 2017. Vol. 222, № 1. P. 31-38
ISSN: 0171-2985
DOI: 10.1016/j.imbio.2015.09.011
Popis: 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+/stabilin-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.
Databáze: OpenAIRE