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The in vivo modulatory effects of an anterior-chamber microenvironment on uveal melanoma
  1. H S Mudhar1,2,
  2. E Saunders2,
  3. P Rundle4,
  4. I G Rennie3,
  5. K Sisley3
  1. 1
    National Specialist Ophthalmic Pathology Service, Royal Hallamshire Hospital, Sheffield, UK
  2. 2
    Department of Histopathology, E-Floor, Royal Hallamshire Hospital, Sheffield, UK
  3. 3
    University of Sheffield, Academic Unit of Ophthalmology and Orthoptics, K-Floor, School of Medicine and Biomedical Sciences, Sheffield, UK
  4. 4
    Department of Ophthalmology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
  1. Dr H S Mudhar, Department of Histopathology, E-Floor, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, UK; hardeep.mudhar{at}sth.nhs.uk

Abstract

Background: Primary melanoma of the iris, for reasons unknown has a lower metastatic rate compared with primary ciliary-body melanoma. Six histology cases of ciliary-body melanoma were identified that had spread onto the iris surface and into the stroma, representing a change in tumour microenvironment from aqueous humour non-exposure (ciliary-body component) to aqueous humour exposure (iris surface component). This provided an ideal paradigm for investigating the effects of different environments on melanoma.

Method: Conventional light microscopy was performed on stained paraffin sections of the identified cases, followed by immunohistochemistry to cell cycle proteins p27 and Cyclin D1. Fluorescence in situ hybridisation (FISH) analysis was conducted on the paraffin sections for changes of chromosomes 3 and 8, associated with poor uveal melanoma prognosis.

Results: Iris surface melanoma cells were smaller compared with the adjacent deeper iris stromal melanoma cells and with those in the ciliary body. Fewer iris surface melanoma cells expressed Cyclin D1 protein, but more expressed p27 protein, compared with the larger iris stromal melanoma cells (paired Wilcoxon signed ranks test: Cyclin D1 p = 0.028; p27 p = 0.046) and with the ciliary-body melanoma cells (paired Wilcoxon signed ranks test: Cyclin D1 p = 0.028; p27 p = 0.028). With FISH, chromosome 3 and 8 alterations were less common among the iris surface melanoma cells than the deeper iris stromal melanoma cells and the ciliary-body melanoma cells, which were consistently characterised by a relative genetic imbalance for chromosomes 3 and 8.

Conclusions: These data suggest that there are tumour-modulatory factors within the anterior chamber environment that probably select populations of ciliary-body melanoma cells, with a less aggressive, better-differentiated status. Furthermore, it may help explain why iris melanomas generally have a less aggressive course than ciliary-body and choroidal melanomas.

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Footnotes

  • Funding: The work was supported by grants from Yorkshire Eye Research (003) and from Trent Regional Health (RBF00XX5). The overall work was supported by Yorkshire Cancer Research, UK.

  • Competing interests: None.

  • Ethics approval: Ethics approval was provided by Sheffield Teaching Hospitals NHS Trust local research ethics committee (SSERC 94/247 and STH 13738).

  • Patient consent: Obtained.

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