title: Monosomy of chromosome 3 and an inflammatory phenotype occur together in uveal melanoma.
abstract: OBJECTIVE
  In uveal melanoma, different predictors of poor prognosis have been identified, including monosomy of chromosome 3, HLA expression, and the presence of infiltrating leukocytes and macrophages. Each of these parameters can be used to differentiate prognostically the favorable tumors from the unfavorable ones, and thus the hypothesis for the present study was that they are related, and that monosomy of chromosome 3 occurs in the same tumors as the unfavorable inflammatory phenotype.
  
  
  METHODS
  Tumor tissue was obtained from 50 cases of uveal melanoma treated between 1999 and 2004. After enucleation, nuclei were isolated from paraffin-embedded tissue for fluorescence in situ hybridization, to determine the chromosome 3 copy number. Each tumor-containing globe was further processed for conventional histopathologic examination and for immunohistochemical analysis with HLA class I and II-specific antibodies and with macrophage marker CD68.
  
  
  RESULTS
  Of 50 uveal melanomas, 62% (31/50) were categorized as having monosomy of chromosome 3. Monosomy 3 was associated with the presence of epithelioid cells, an increased density of tumor-infiltrating macrophages, and a higher HLA class I and II expression. Survival analyses showed a correlation between monosomy 3 and decreased survival and identified monosomy 3, ciliary body involvement, and largest basal tumor diameter as the best prognostic markers.
  
  
  CONCLUSIONS
  Monosomy 3 in uveal melanoma is associated with the presence of an inflammatory phenotype, consisting of a high HLA class I and II expression as well as an increased number of tumor-infiltrating macrophages. In a multivariate Cox regression analysis, the presence of monosomy 3 was one of the best prognostic markers of metastatic disease and survival, although the follow-up time was short.
authors.affiliation: Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Willem
authors.initials: W
authors.lastname: Maat
authors.forename: Long V
authors.initials: LV
authors.lastname: Ly
authors.forename: Ekaterina S
authors.initials: ES
authors.lastname: Jordanova
authors.forename: Didi
authors.initials: D
authors.lastname: de Wolff-Rouendaal
authors.forename: Nicoline E
authors.initials: NE
authors.lastname: Schalij-Delfos
authors.forename: Martine J
authors.initials: MJ
authors.lastname: Jager
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D008264:Macrophages / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D009006:Monosomy / Q000235:genetics*; D014604:Uveal Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C067980:CD68 antigen, human; D000097382:CD68 Molecule