title: Infiltrating macrophages in extratumoural tissues after brachytherapy of uveal melanoma.
abstract: OBJECTIVE
  To compare distribution of macrophages in extratumoural ocular tissues in enucleated eyes with irradiated and nonirradiated uveal melanomas to find out how irradiation affects distribution of macrophages so as to gain insight into their potential routes of migration and changes in local inflammatory responses.
  
  
  METHODS
  Thirty-four matched pairs of primarily enucleated nonirradiated and secondarily enucleated irradiated eyes with choroidal and ciliary body melanoma were stained with mAb PG-M1, and the extratumoural immunopositive elements were counted under the microscope. Main outcome variables were the number of macrophages in the sclera underlying the tumour, in the choroid adjacent to the tumour, and in the ciliary body. The number of macrophage aggregates in the anterior ipsi- and contralateral episclera adjacent to the limbus was also counted.
  
  
  RESULTS
  Macrophages were more numerous within the sclera under the tumour in irradiated eyes when compared to primarily enucleated eyes (median 1514 versus 619/mm², p = 0.0001), and more aggregates of episcleral macrophages adjacent to the limbus were found after irradiation (ipsilateral side, median 132 versus 0, p = 0.0034; contralateral side, median 79 versus 0, p = 0.014). In primarily enucleated eyes, increasing numbers of tumour-infiltrating macrophages were associated with presence of higher numbers of macrophages in the ciliary body (p = 0.003) and the adjacent choroid (p = 0.044), whereas in the irradiated eyes, increasing numbers of tumour-infiltrating macrophages (p = 0.010) and increasing extent of necrosis (p < 0.001) were associated with higher numbers of intrascleral macrophages underlying the tumour.
  
  
  CONCLUSIONS
  Resident macrophages are present in extratumoural tissues in eyes with uveal melanoma. Brachytherapy may alter their route of migration and increase the number of macrophages in the sclera and episclera. Histopathologically detectable episcleral aggregates of macrophages adjacent to the limbus are detected predominantly after irradiation, a population of which is clinically visible as episcleral deposits after irradiation.
authors.affiliation: Ocular Oncology Service, Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland. paivi.toivonen@hus.fi
authors.forename: Päivi
authors.initials: P
authors.lastname: Toivonen
authors.forename: Tero
authors.initials: T
authors.lastname: Kivelä
mesh_terms: D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D001918:Brachytherapy; D016022:Case-Control Studies; D002452:Cell Count; D002465:Cell Movement; D002829:Choroid / Q000276:immunology; D002924:Ciliary Body / Q000276:immunology; D015353:Eye Enucleation; D006801:Humans; D007124:Immunoenzyme Techniques; D008264:Macrophages / Q000473:pathology*; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy; D008833:Microcirculation; D012590:Sclera / Q000276:immunology; D014604:Uveal Neoplasms / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy; D000097382:CD68 Molecule
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C429108:107-1A4 monoclonal antibody; C067980:CD68 antigen, human; D000097382:CD68 Molecule