title: Microcirculation and tumor-infiltrating macrophages in choroidal and ciliary body melanoma and corresponding metastases.
abstract: OBJECTIVE
  To investigate the relationship between progression to hepatic metastasis and tumor-infiltrating macrophages and microcirculation attributes in uveal melanoma, a cancer that almost invariably disseminates hematogenously to the liver.
  
  
  METHODS
  A cross-sectional histopathologic analysis of 48 hepatic metastases and corresponding primary choroidal and ciliary body melanomas was conducted, by using statistical tests appropriate for paired data. Main outcome measures were the number and type of CD68-immunopositive, tumor-infiltrating macrophages, extravascular matrix loops and networks identified with periodic acid-Schiff stain, and microvascular density (MVD) counted as the number of discrete structures labeled by monoclonal antibody QBEND/10 to the CD34 epitope.
  
  
  RESULTS
  Hepatic metastases had a significantly lower grade of pigmentation (P < 0.0001), more frequent epithelioid cells (P = 0.0027), more intermediate and dendritic types of CD68-immunopositive macrophages than round ones (P = 0.0031), and a higher MVD (median difference, 15 counts more/0.313 mm2, P = 0.0003) than the primary uveal melanomas that spawned the metastases. The frequency of tumors with extravascular loops and networks did not increase on metastasizing. The survival of the patient after diagnosis of disseminated disease tended to be shorter if hepatic metastases had a high MVD (P = 0.098), adjusting for the size of the specimen.
  
  
  CONCLUSIONS
  Of the markers studied, the presence of epithelioid cells and MVD most closely parallel progression of uveal melanoma from primary tumor to metastasis. These two tumor characteristics may be interrelated, and high MVD may help to predict survival after detection of hepatic metastases. The results also suggest that the grade of pigmentation and morphologic type of tumor-infiltrating macrophages are interrelated.
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: Teemu
authors.initials: T
authors.lastname: Mäkitie
authors.forename: Emma
authors.initials: E
authors.lastname: Kujala
authors.forename: Tero
authors.initials: T
authors.lastname: Kivelä
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002465:Cell Movement; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000098:blood supply* / Q000401:mortality / Q000556:secondary*; D008833:Microcirculation; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology; D015996:Survival Rate; D014604:Uveal Neoplasms / Q000098:blood supply* / Q000401:mortality / Q000473:pathology*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; C067980:CD68 antigen, human; D000097382:CD68 Molecule