Histologic and immunohistochemical predictors of clinical behavior for feline diffuse iris melanoma

K. Tomo Wiggans, Christopher M. Reilly, Philip H Kass, David J Maggs

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Objective: To determine histologic and immunohistochemical predictors of metastasis of feline diffuse iris melanoma (FDIM). Animals: Globes from 47 client-owned cats enucleated for FDIM between January 1985 and December 2013. Procedures: 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.

Original languageEnglish (US)
Pages (from-to)44-55
Number of pages12
JournalVeterinary Ophthalmology
Volume19
DOIs
StatePublished - Jul 1 2016

Fingerprint

Felidae
Iris
melanoma
Melanoma
metastasis
cats
Neoplasm Metastasis
MART-1 Antigen
Cats
Cadherins
cadherins
Necrosis
Eye Enucleation
necrosis
Mitotic Index
Veterinarians
Hematoxylin
Eosine Yellowish-(YS)
Proportional Hazards Models
Mitosis

Keywords

  • B-Raf
  • E-cadherin
  • feline diffuse iris melanoma
  • melan-A
  • pheomelanin
  • PNL2

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Histologic and immunohistochemical predictors of clinical behavior for feline diffuse iris melanoma. / Wiggans, K. Tomo; Reilly, Christopher M.; Kass, Philip H; Maggs, David J.

In: Veterinary Ophthalmology, Vol. 19, 01.07.2016, p. 44-55.

Research output: Contribution to journalArticle

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abstract = "Objective: To determine histologic and immunohistochemical predictors of metastasis of feline diffuse iris melanoma (FDIM). Animals: Globes from 47 client-owned cats enucleated for FDIM between January 1985 and December 2013. Procedures: 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.",
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N2 - Objective: To determine histologic and immunohistochemical predictors of metastasis of feline diffuse iris melanoma (FDIM). Animals: Globes from 47 client-owned cats enucleated for FDIM between January 1985 and December 2013. Procedures: 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.

AB - Objective: To determine histologic and immunohistochemical predictors of metastasis of feline diffuse iris melanoma (FDIM). Animals: Globes from 47 client-owned cats enucleated for FDIM between January 1985 and December 2013. Procedures: 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.

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