Investigation of prognostic indicators for human uveal melanoma as biomarkers of canine uveal melanoma metastasis

Malho, Pedro; Dunn, Kelli Bullard; Donaldson, David I.; Dubielzig, Richard R.; Birand, Zeynap; Starkey, Mike

doi:10.1111/jsap.12141

Cited by 25 publications

(41 citation statements)

References 29 publications

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“…Although rare cases of spontaneous intraocular melanomas have been reported in different animal species, including dogs [351, 352], cats [353, 354], horses [355], and cattle [356], no spontaneous UMs were reported in mice, which would represent the most convenient species. Syngeneic transplantable and transgenic models of UM allow investigating the interaction between the host immune system and the tumor.…”

Section: Animal Modelsmentioning

confidence: 99%

The biology of uveal melanoma

Amaro

Gangemi

Piaggio

et al. 2017

Cancer Metastasis Rev

184

193

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Uveal melanoma (UM), a rare cancer of the eye, is distinct from cutaneous melanoma by its etiology, the mutation frequency and profile, and its clinical behavior including resistance to targeted therapy and immune checkpoint blockers. Primary disease is efficiently controlled by surgery or radiation therapy, but about half of UMs develop distant metastasis mostly to the liver. Survival of patients with metastasis is below 1 year and has not improved in decades. Recent years have brought a deep understanding of UM biology characterized by initiating mutations in the G proteins GNAQ and GNA11. Cytogenetic alterations, in particular monosomy of chromosome 3 and amplification of the long arm of chromosome 8, and mutation of the BRCA1-associated protein 1, BAP1, a tumor suppressor gene, or the splicing factor SF3B1 determine UM metastasis. Cytogenetic and molecular profiling allow for a very precise prognostication that is still not matched by efficacious adjuvant therapies. G protein signaling has been shown to activate the YAP/TAZ pathway independent of HIPPO, and conventional signaling via the mitogen-activated kinase pathway probably also contributes to UM development and progression. Several lines of evidence indicate that inflammation and macrophages play a pro-tumor role in UM and in its hepatic metastases. UM cells benefit from the immune privilege in the eye and may adopt several mechanisms involved in this privilege for tumor escape that act even after leaving the niche. Here, we review the current knowledge of the biology of UM and discuss recent approaches to UM treatment.

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Section: Animal Modelsmentioning

confidence: 99%

The biology of uveal melanoma

Amaro

Gangemi

Piaggio

et al. 2017

Cancer Metastasis Rev

184

193

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“…Increased label intensity of melan‐A and E‐cadherin was associated with an increased risk of metastasis, and homogenous labeling of PNL2 was associated with a decreased risk of metastasis. Such validated molecular assays could be used to guide decision‐making and help clinicians preserve visual and comfortable eyes . With further investigations, it is possible that such immunohistochemical markers could be applied to incisional biopsy samples, iris aspirates, and aqueocentesis samples …”

Section: Discussionmentioning

confidence: 99%

“…Such validated molecular assays could be used to guide decision-making and help clinicians preserve visual and comfortable eyes. 2,17,18 With further investigations, it is possible that such immunohistochemical markers could be applied to incisional biopsy samples, iris aspirates, and aqueocentesis samples. 2 The terminology used in cases of feline iris hyperpigmentation can be controversial and confusing, and a proposed review of the current nomenclature is beyond the scope of, and is not the intention of, this article.…”

Section: Discussionmentioning

confidence: 99%

Iris biopsy to investigate feline iris hyperpigmentation

Featherstone

Scurrell²,

Rhodes³

et al. 2019

Veterinary Ophthalmology

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Objective To evaluate the benefit of iris biopsy in cats with iris hyperpigmentation to differentiate melanosis from early feline diffuse iris melanoma (FDIM). Methods The medical records of cats with unilateral iris hyperpigmentation that had undergone iris biopsy between February 2013 and September 2016 at Willows Veterinary Centre & Referral Service were reviewed. Results Seven cats with unilateral iris hyperpigmentation were included in this retrospective study. The biopsy procedure was performed under general anesthesia (n = 7) with neuromuscular blockade (n = 6) following pre‐operative topical miotic therapy (n = 5). One to six biopsy samples per eye were harvested from areas of hyperpigmentation. The samples were partial thickness (n = 4 eyes) and full thickness (n = 3 eyes). Complications were minor: mild intra‐operative hemorrhage (n = 4), fibrin clot (n = 2), corneal ulcer (n = 1), post‐operative ocular hypertension (n = 1), dyscoria (n = 1), and pseudopolycoria (n = 2). The first biopsy was diagnostic in six cats; a repeat biopsy was necessary in one cat. Histopathology was consistent with melanosis in five cats and with early FDIM in two cats. Screening for signs of metastatic disease (thoracic computed tomography and abdominal ultrasonography) was negative in the two cats with a preliminary diagnosis of early FDIM. Subsequent enucleation and histopathology confirmed the initial diagnosis in both cases. Conclusions Iris biopsy in cats with iris hyperpigmentation can be beneficial to differentiate melanosis from early FDIM and thereby help to justify the decision for early enucleation.

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“…Although very attractive, this classification is not appropriate for canine and feline melanomas due to differences in tumor behavior, localization, and cell types . Various studies attempted to correlate microscopic features with clinical behavior to determine aggressiveness and malignancy of melanomas in dogs and cats . Tumor extension, tumor size, and mitotic index were found to be unreliable predictors of survival for dogs affected by uveal melanoma .…”

Section: Discussionmentioning

confidence: 99%

A case of primary choroidal malignant melanoma in a cat

Bourguet

Piccicuto

Donzel

et al. 2014

Veterinary Ophthalmology

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This report describes the clinical presentation, diagnosis, histological lesions, and prognosis of a primary choroidal malignant melanoma in a 15-year-old cat. The animal was presented for unilateral blindness. On ocular examination, a raised pigmented mass protruding from the posterior pole into the vitreous body was observed by diffuse transillumination and indirect ophthalmoscopy. Ocular ultrasound and computer tomography (CT) scan confirmed localization of the tumor to the posterior segment. The diagnosis of primary choroidal melanoma was confirmed by histopathology after enucleation. To our knowledge, this is the first reported case of a feline malignant melanoma with a primary choroidal localization without iris involvement.

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Investigation of prognostic indicators for human uveal melanoma as biomarkers of canine uveal melanoma metastasis

Cited by 25 publications

References 29 publications

The biology of uveal melanoma

The biology of uveal melanoma

Iris biopsy to investigate feline iris hyperpigmentation

A case of primary choroidal malignant melanoma in a cat

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