title: Immunohistochemical and molecular pathology of ocular uveal melanocytoma: evidence for somatic GNAQ mutations.
abstract: OBJECTIVE
  Intraocular melanocytoma is a rare naevus variant that can be located at the optic disc or within the uvea, and belongs to the group of non-epithelial-associated melanocytic lesions. We wanted to gain an understanding of the role of GNAQ, GNA11 and BRAF V600E in the pathogenesis of uveal melanocytoma and in cases of transformation to uveal melanoma and also to perform a differential immunohistochemical study comparing melanocytoma with uveal melanoma.
  
  
  RESULTS
  Two patients were identified with melanocytoma, one of which had transformed to melanoma. In the latter case, the melanocytoma exhibited an immunophenotype that featured nuclear p27 and no HMB45 staining, with very low Cyclin D1 expression compared with the melanoma that featured little nuclear but more cytoplasmic p27 positivity, much higher Cyclin D1 expression and HMB45 positivity. The melanocytomas were negative for CD68 allowing distinction from melanophages. Both melanocytomas and the melanoma harboured mutations in GNAQ, with no mutations of GNA11 or BRAF V600E.
  
  
  CONCLUSIONS
  GNAQ mutations are present in uveal melanocytomas and in a case of transformation to melanoma, implicating GNAQ-dependent mitogen activation signals, in the pathogenesis of uveal melanocytoma. This assists in explaining why a proportion of uveal melanocytoma can transform to uveal melanoma, known to harbour high-frequency GNAQ mutations at exon 5, codon 209.
authors.affiliation: National Specialist Ophthalmic Pathology Service, Department of Histopathology, Royal Hallamshire Hospital, Sheffield, UK. hardeep.mudhar@sth.nhs.uk
authors.forename: Hardeep Singh
authors.initials: HS
authors.lastname: Mudhar
authors.forename: Rachel
authors.initials: R
authors.lastname: Doherty
authors.forename: Abdulazeez
authors.initials: A
authors.lastname: Salawu
authors.forename: Karen
authors.initials: K
authors.lastname: Sisley
authors.forename: Ian G
authors.initials: IG
authors.lastname: Rennie
mesh_terms: D000293:Adolescent; D000328:Adult; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D019938:Cyclin D1 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D058965:MART-1 Antigen / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058950:Melanoma-Specific Antigens / Q000378:metabolism; D009154:Mutation; D009508:Nevus, Pigmented / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012189:Retrospective Studies; D014604:Uveal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058951:gp100 Melanoma Antigen
chemical_list: C554062:GNA11 protein, human; C554061:GNAQ protein, human; D044385:GTP-Binding Protein alpha Subunits; D058965:MART-1 Antigen; C548667:MLANA protein, human; D058950:Melanoma-Specific Antigens; C548637:PMEL protein, human; D058951:gp100 Melanoma Antigen; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D048493:Proto-Oncogene Proteins B-raf; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
keywords: Eye (Globe); Neoplasia; Pathology