title: Histologic and immunohistochemical predictors of clinical behavior for feline diffuse iris melanoma.
abstract: OBJECTIVE
  To determine histologic and immunohistochemical predictors of metastasis of feline diffuse iris melanoma (FDIM).
  
  
  METHODS
  Globes from 47 client-owned cats enucleated for FDIM between January 1985 and December 2013.
  
  
  METHODS
  Hematoxylin and eosin-stained sections were evaluated for neoplastic invasiveness and cell morphology, necrosis within the neoplasm, inflammation, and glaucoma. Sections were immunolabeled with antibodies against melan-A, PNL2, E-cadherin, or B-Raf, and label intensity, percentage of labeled cells, and label homogeneity were semi-quantitatively graded. Medical records were evaluated, and referring veterinarians and clients were contacted to determine whether cats developed metastasis following enucleation. The log-rank test or Cox proportional hazards model was used to determine associations between histologic or immunohistochemical parameters and metastasis.
  
  
  RESULTS
  Metastasis was suspected or confirmed in 9/47 (19%) cats. Extrascleral extension, necrosis within the neoplasm, a mitotic index of >7 mitoses in 10 high-power (×400) fields, choroidal invasion, and increased E-cadherin and melan-A label intensity were each associated with increased rate of metastasis. PNL2 label homogeneity was associated with decreased rate of metastasis. Decreased PNL2 label intensity and an increasing percentage of neoplastic cells labeled for melan-A each approached significance for increased rate of metastasis.
  
  
  CONCLUSIONS
  We report four histologic and three immunohistochemical parameters helpful in determining cats at risk of metastasis of FDIM. Further studies should determine if B-Raf mutations identified in human malignant melanomas are found in cats with FDIM and assess benefits of adjunctive therapy following enucleation of eyes with FDIM bearing poor prognostic indicators.
authors.affiliation: William R. Pritchard Veterinary Medical Teaching Hospital, University of California, Davis, CA, 95616, USA.
authors.forename: K Tomo
authors.initials: KT
authors.lastname: Wiggans
authors.affiliation: Departments of Pathology, Microbiology, and Immunology, University of California, Davis, CA, 95616, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Reilly
authors.affiliation: Population Health and Reproduction, University of California, Davis, CA, 95616, USA.
authors.forename: Philip H
authors.initials: PH
authors.lastname: Kass
authors.affiliation: Surgical and Radiological Sciences, University of California, Davis, CA, 95616, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Maggs
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002371:Cat Diseases / Q000473:pathology*; D002415:Cats; D005260:Female; D007150:Immunohistochemistry / Q000662:veterinary; D015811:Iris Neoplasms / Q000473:pathology / Q000662:veterinary*; D008297:Male; D008545:Melanoma / Q000473:pathology / Q000556:secondary / Q000662:veterinary*; D009362:Neoplasm Metastasis; D014604:Uveal Neoplasms / Q000473:pathology / Q000556:secondary / Q000662:veterinary*; D000098943:Uveal Melanoma
chemical_list: D014408:Biomarkers, Tumor
keywords: B-Raf; E-cadherin; PNL2; feline diffuse iris melanoma; melan-A; pheomelanin