Giant foam-like macrophages in advanced ovarian cancer

Abstract

Introduction. Ovarian cancer (OC) is the third most common gynecological cancer with the worst prognosis and highest mortality rate. The progression of OC can be accompanied by the detrimental functions of the components of the tumor microenvironment, including tumor-associated macrophages (TAMs).The purpose of the study to analyze distribution and morphological phenotype of TAMs in tumor tissue of patients with high-grade serous ovarian cancer (HGSOC).Material and methods. Formalin fixed paraffin embedded tissue sections were obtained from ovarian cancer patients after tumor resection. The protein expression of general macrophage marker CD68 and M2-like markers CD206, CD163 and stabilin-1, belonging to scavenger receptors, was analysed by immunohistochemical staining in tumor tissue. Histological assessment of TAM distribution was performed by pathologist. Immunofluorescent analysis/confocal microscopy was applied to establish the co-expression of CD68 with the main macrophage scavenger receptors.Results. We were able to find giant CD 68-positive macrophages with foamy cytoplasm in ovarian tumor tissue. The accumulation of these tams was specific only for patients with advanced stage (IIIC and IV stages). The presence of foamlike tams had a statistical tendency to be associated with ovarian cancer progression, including metastasis and recurrence. The distribution of stabilin-1-positive macrophages was matched to CD68 expression in almost all cases, as was shown by IHC. Confocal microscopy confirmed that stabilin-1 was expressed in at least 50 % of giant tams. If analysis of tumor samples also demonstrated co-expression of other scavenger receptors, CD163 and CD36, in foam-like cells. Similar to IHC, in most samples the expression of CD206 in tams of foam-like morphology was limited.Conclusion. For the first time we demonstrated the accumulation of giant macrophages with fluffy foam cytoplasm in the tumor tissue of treated patients with advanced ovarian cancer. Such macrophages express diverse scavenger receptors (stabilin-1, CD163, CD 36), thus indicating a high clearance activity of giant TAMs.