3 Original article Folia Med. Fac. Med. Univ. Saraeviensis 2019; 54(1): 3-9 foliamedica.mf.unsa.ba Macrophages polarization and density of tumor-associated dendritic cells correlated with depth of invasion in gastric adenocarcinoma Edina Lazović Salčin*, Svjetlana Radović, Mirsad Dorić, Suada Kuskunović-Vlahovljak, Nina Čamdžić, Mirsad Babić Department of Pathology, Faculty of Medicine, University of Sarajevo, Sarajevo, Bosnia and Herzegovina *Corresponding author Edina Lazović Salčin Department of Pathology Faculty of Medicine University of Sarajevo Čekaluša 90, 71000 Sarajevo Bosnia and Herzegovina E-mail: edina.lazovic@mf.unsa.ba Abstract Introduction: Tumor-associated macrophages (TAM) are the most common infammatory cells in the tumor microenviron- ment (TM). As a response to microenvironmental signals, they polarize into tumor resisting M1 or promoting M2 macrophag- es. TAM and tumor-associated dendritic cells (TADC) can either promote tumor growth and tissue invasiveness or have anti-tumor activity. Te aim of the study was the examination of prognostic value in the individual cell population in TM and their correlation with clinicopathological parameters of gastric cancer. Materials and Methods: Te study analyzed 60 samples of gas- tric cancer, known status of regional lymph nodes and without dissemination at the time of diagnosis. Te control group was normal gastric tissue samples. Traditional parameters of bio- logical aggressiveness, tumor size, histological grade, and lym- phovascular invasion, are determined after standard hematoxy- lin-eosin staining. TAM and TADS have been evaluated using the immunohistochemical method with CD68 (TAM), TNFa (TAM-M1), CD163 (TAM-M2), and S100 (TADC) antibod- ies. Expression evaluation of the tissue antigen was carried out by semiquantitative methods. Results: Tere were statistically signifcant diferences of TAM density (P <0.001) with M1 (P <0.001) and M2 (P <0.01) po- larization in cancer tissue compared to the control group. Statis- tically, signifcant positive linear correlation between the num- ber of CD68 TAM and TAM-M1 was observed (P <0.001). In the cancer tissue samples, with increasing tumor size (pT), increased TADC and TAM M1 density, with no statistically sig- nifcance (P> 0.05). Conclusion: TAMs and TADC have shown potential as bio- markers for evaluating the gastric cancer staging and progres- sion. Tey showed promising prediction in depth of invasion, histological grade of tumor and tumor size. Keywords: gastric cancer, tumor microenvironment, TAM, TAM-M1/M2, TADC © 2019 Folia Medica Facultatis Medicinae Universitatis Saraeviensis. All rights reserved. Introduction Te interaction between carcinoma cells and their mi- croenvironment is crucial for tumor progression and modulation of invasive activity. Many studies show that numerical and functional variations of tumor-associat- ed macrophages (TAM) and tumor-associated dendrit- ic cells (TADC) may or may not be in correlation with clinicopathological parameters, which means parame- ters of biological aggressiveness (1). TAM and i TADC show dual potential: they can promote tumor growth and invasion, afect the length of patients survival, but also, they can show antitumor activity. So, overcome the suppressive or immunogenic character, depending on nteraction between these and cancer cells. TAM has a tendency to be polarized into proinfam- matory M1 and anti-infammatory M2 macrophages. Most of them are M2 polarized (2). Tey inhibit the infammation, remodel connective tissue, recruit fbro- blasts, promote neoangiogenesis and show tumoricidal activity (3). M1 macrophages show a protective char- acter in tumor-genesis by activating tumor-destroying mechanisms and antagonizing activation of various macrophages M2 which are obviously involved in tu- mor suppression by adaptive immune response and the promotion of tumor growth, invasiveness, metas- tasis, stromal remodeling and angiogenesis (2). TAMs are generally considered to be allies in the process of progression of the disease into several types of can- cer (4,5,6,7,8), but their role in the gastric and colon cancer is still poorly understood and investigated (9). TADC belong to a monocyte-macrophage cell line which strongly expresses the S100 protein (10). Tey are a specialized group of cells and play a key role in the induction and maintenance of antitumor immu- nity, but in the tumor microenvironment (TM) their antigen presenting function may be inefective or com- pletely lost. In this way, the infltration of tumor tissue with TADC is refected in the local immune response. TADC infltration of primary, esophageal, nasopha-