Macrophages in Regressed and Progressed Uveal Melanoma

This dissertation is based on the following original publications on non-irradiated, irradiated, and metastatic uveal melanoma. The original publications in the text will be referred to by their Roman numerals I-IV: in regressed and partially regressed irradiated choroidal and ciliary body melanomas.infiltrating macrophages in choroidal and ciliary body melanoma and corresponding metastases. III Toivonen P and Kivelä T. Pigmented episcleral deposits following brachytherapy of uveal melanoma. IV Toivonen P and Kivelä T. Infiltrating macrophages in extratumoral tissues after brachytherapy of uveal melanoma. Acta Ophthalmol. (in press) Abbreviations 8 ABBREVIATIONS ABC Avidin-biotinylated peroxidase complex ACAID Anterior chamber-associated immune deviation APC Antigen-presenting cell BSA Bovine serum albumin CI Confidence interval COMS The Collaborative Ocular Melanoma Study CT Computed tomography DAB Diaminobenzidine DC Dendritic cell ECM Extracellular matrix EVM Extravascular matrix EMAP Endothelial monocyte-activating polypeptide EORTC European Organization for Research and Treatment of Cancer FAG Fluorescein angiography FNAB Fine needle aspiration biopsy HLA Human leukocyte antigen HR Hazard ratio HUCH Helsinki University Central Hospital ICAM Intracellular adhesion molecule IGF Insulin-like growth factor IHC Immunohistochemistry IOP Intraocular pressure LBD Largest basal diameter mAb Monoclonal antibody MCP Monocyte chemotactic protein M-CSF Macrophage colony stimulating factor MIF Macrophage-migration-inhibitory factor MLN Mean diameter of the ten largest nucleoli MMP Matrix metalloproteinase MRI Magnetic resonance imaging MVD Microvascular density N/A Not applicable NK Natural killer OCT Optical coherence tomography PAD Pathologic-anatomical diagnosis PAS Periodic acid-Schiff PBS Phosphate-buffered saline RPE Retinal pigment epithelium TNF Tumor necrosis factor alpha TNM Tumor, node, metastasis classification, a cancer staging system TTT Transpupillary thermotherapy US Ultrasonography UV Ultraviolet VEGF Vascular endothelial growth factor Abstract 9 1. ABSTRACT This study was undertaken to better understand the behavior of macrophages during regression and progression of uveal melanoma. The study was divided into three histopathological parts (I, II, and IV) and one clinical part (III). The first study (I) aimed to find out how irradiation and subsequent regression of the tumor tissue affects the number and type of tumor-infiltrating macrophages and microcirculation attributes in uveal melanoma. The second study (II) was carried out to understand the relationship between tumor-infiltrating macrophages and microcirculation attributes in primary uveal melanoma and corresponding hepatic metastases. The purpose was to find out how progression of the tumor affects these variables and to investigate whether microvascular attributes influence the survival. The third study (III) described the evolution and addressed the origin of pigmented episcleral deposits found after brachytherapy and investigated their relationship …