title: Modelling uveal melanoma.
abstract: OBJECTIVE
  There has been no consistent pattern reported on how mortality for uveal melanoma varies with age. This information can be useful to model the complexity of the disease. The authors have examined ocular cancer trends, as an indirect measure for uveal melanoma mortality, to see how rates vary with age and to compare the results with their other studies on predicting metastatic disease.
  
  
  METHODS
  Age specific mortality was examined for England and Wales, the USA, and Canada. A log-log model was fitted to the data. The slopes of the log-log plots were used as measure of disease complexity and compared with the results of previous work on predicting metastatic disease.
  
  
  RESULTS
  The log-log model provided a good fit for the US and Canadian data, but the observed rates deviated for England and Wales among people over the age of 65 years. The log-log model for mortality data suggests that the underlying process depends upon four rate limiting steps, while a similar model for the incidence data suggests between three and four rate limiting steps. Further analysis of previous data on predicting metastatic disease on the basis of tumour size and blood vessel density would indicate a single rate limiting step between developing the primary tumour and developing metastatic disease.
  
  
  CONCLUSIONS
  There is significant underreporting or underdiagnosis of ocular melanoma for England and Wales in those over the age of 65 years. In those under the age of 65, a model is presented for ocular melanoma oncogenesis requiring three rate limiting steps to develop the primary tumour and a fourth rate limiting step to develop metastatic disease. The three steps in the generation of the primary tumour involve two key processes-namely, growth and angiogenesis within the primary tumour. The step from development of the primary to development of metastatic disease is likely to involve a single rate limiting process.
authors.affiliation: Directorate of Ophthalmology, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH.
authors.forename: A J
authors.initials: AJ
authors.lastname: Foss
authors.forename: I A
authors.initials: IA
authors.lastname: Cree
authors.forename: P J
authors.initials: PJ
authors.lastname: Dolin
authors.forename: J L
authors.initials: JL
authors.lastname: Hungerford
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002170:Canada / Q000453:epidemiology; D004739:England / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008545:Melanoma / Q000401:mortality*; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D016017:Odds Ratio; D014481:United States / Q000453:epidemiology; D014604:Uveal Neoplasms / Q000401:mortality* / Q000556:secondary; D014852:Wales / Q000453:epidemiology