Amount of CD68+ Tumor Associated Macrophages in Gaps of Ductal Tumor Structures Negatively Correlates with Lymphatic Metastases in Human Breast Cancer - ICMS2015 Abstract Submission Form Tumor Microenvironment Conference

Mikhail Buldakov ^1,2 Marina Zavyalova ^1,2,3 Nadejda Krakhmal ^2,3 Nadejda Telegina ³ Sergey Vtorushin ^2,3 Vladimir Riabov ⁴ Shuiping Yin ⁴ Nadezhda Cherdyntseva ^1,2 Julia Kzhyshkowska ^1,4

¹Laboratory for translational cellular and molecular biomedicine, Tomsk State University, Russia
²Laboratory of mollecular oncology and immunology, Tomsk Cancer Research Institute, Russia
³Department of Pathological Anatomy, Siberian State Medical University, Russia
⁴Department of Innate Immunity and Tolerance, Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Germany

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. Patients with nonspecific invasive breast cancer T1-4N0-3M0 from Tomsk Cancer Research Institute 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 phenotype 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.