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Review
. 2019 Jun 30;10(7):501.
doi: 10.3390/genes10070501.

Canine Melanomas as Models for Human Melanomas: Clinical, Histological, and Genetic Comparison

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Free PMC article
Review

Canine Melanomas as Models for Human Melanomas: Clinical, Histological, and Genetic Comparison

Anaïs Prouteau et al. Genes (Basel). .
Free PMC article

Abstract

Despite recent genetic advances and numerous ongoing therapeutic trials, malignant melanoma remains fatal, and prognostic factors as well as more efficient treatments are needed. The development of such research strongly depends on the availability of appropriate models recapitulating all the features of human melanoma. The concept of comparative oncology, with the use of spontaneous canine models has recently acquired a unique value as a translational model. Canine malignant melanomas are naturally occurring cancers presenting striking homologies with human melanomas. As for many other cancers, dogs present surprising breed predispositions and higher frequency of certain subtypes per breed. Oral melanomas, which are much more frequent and highly severe in dogs and cutaneous melanomas with severe digital forms or uveal subtypes are subtypes presenting relevant homologies with their human counterparts, thus constituting close models for these human melanoma subtypes. This review addresses how canine and human melanoma subtypes compare based on their epidemiological, clinical, histological, and genetic characteristics, and how comparative oncology approaches can provide insights into rare and poorly characterized melanoma subtypes in humans that are frequent and breed-specific in dogs. We propose canine malignant melanomas as models for rare non-UV-induced human melanomas, especially mucosal melanomas. Naturally affected dogs offer the opportunity to decipher the genetics at both germline and somatic levels and to explore therapeutic options, with the dog entering preclinical trials as human patients, benefiting both dogs and humans.

Keywords: clinics; comparative oncology; dogs; genetics; histology; melanoma; spontaneous model.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Histopathological aspects of human (left) and dog (right) melanoma morphological subtypes. Hematoxylin–Eosin–Safranin (HES) staining of formalin-fixed and paraffin-embedded biopsies. Photo credit: B. Vergier and J. Abadie. (A) “Animal type”: sheets or bundles of highly pigmented large epithelioid to spindle-shaped neoplasic melanocytes; (B) “Simulating (congenital or cellular blue) naevi type”: sheets with a high cellular density of small oval to spindle cells with a small central nucleus containing one to several small nucleoli; (C) “Epithelioid type”: large round to polygonal epithelioid cells with a high amount of variably pigmented cytoplasm and a large nucleus.
Figure 2
Figure 2
Distribution of canine malignant melanomas (n=1652) depending on the anatomical site [34].
Figure 3
Figure 3
Kaplan Meier survival curve of 335 dogs with malignant melanoma. Oral (green line), digital (blue line), and cutaneous (red line) melanomas have significantly different prognosis (p < 0.0001, log-rank test). Oral melanomas have the worse prognosis with a MST (median survival time) of six months, whereas survival times were highest in cutaneous forms (MST not reached). Digital forms seem to have intermediate prognosis with an MST of 11.8 months (Prouteau et al., in preparation [39]).
Figure 4
Figure 4
(A) Breed distribution in a study of 247 canine oral melanomas. Five breeds represent 50% of cases, illustrating the breed predisposition (Prouteau et al., in preparation [39]). (B) Pictures of canine oral melanoma involving the gingiva; that can be pigmented (on the top left) or amelanotic (on the top right). Pictures of human mucosal melanoma (pigmented tumors) arising on the gingiva of the oral cavity. Photo credit: P. De Fornel, A. Dupuy and T. Jouary.
Figure 5
Figure 5
Canine cutaneous melanoma (left) and human nodular melanoma (right). Photo credit: P. Durieux and T. Jouary.
Figure 6
Figure 6
Canine digital melanomas mimic human acral melanomas. Canine digital melanomas can occur on the digit (A) or the footpad (B) and are often ulcerated. Human acral melanomas typically occur on the palmar/plantar surface of the hand/feet (C,D). Photo credit: A. Muller (A), F.A. Fogel (B), A. Dupuy (C), and E. Maubec (D).
Figure 7
Figure 7
Canine uveal melanoma: (A) dog eye with an iridal melanoma; (B) Histological section of a canine uveal melanoma; (C) Melanoma of the ciliary body in a dog. Localized dilation of the episcleral vessels indicating, as in human, a melanoma of the ciliary bodies; (D) Ultrasonography of an affected eye. We notice the high surface echogenicity with rapid decay of this echogenicity Photo credit: P. Durieux.

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