Clinical and Histopathological Characterization of Cutaneous Melanomas in the Melanoblastoma‐Bearing Libechov Minipig Model

Abstract

Spontaneous animal tumors appear to be highly suitable models to study human oncology and cancer therapy. The aim of this study was to characterize the clinical and histological features of hereditary melanocytic lesions found in the French herd of melanoblastoma-bearing Libechov minipigs (MeLiM) and their Duroc crossbreeds. Clinically, we discriminated between three types of melanocytic skin lesions, which offer a lesion continuum from lentigo to metastatic melanomas. More than 70% of these lesions appear on piglets before they are 3 months old and preferentially on homogeneous black coat piglets. The incidence of melanoma reaches 50% in MeLiM. Most of the highly invasive melanomas regressed spontaneously in the first year of the piglet's life and the regression was followed by hair, skin and iris depigmentation. A histopathological study was conducted according to the human melanoma classification. Except for lentigo maligna, we observed the three main types of human melanoma in swine [superficial spreading melanoma (SSM), nodular or unclassified melanoma] with an excess of SSM (59-67%). The histological events leading to total spontaneous regression are chronologically described. The genetic predisposition, the high incidence of melanoma, the clinical and histopathological features similar to the human disease and the high rate of spontaneous regression offer an opportunity to use this model for studying genetic events controlling melanoma development and regression and the biological mechanisms involved in oncogenesis and anti-cancerous self-defense.

Tumour devascularisation as a potential immunotherapeutic strategy

“…8 AA French cohort of MeLiM pigs also exists in which the rate of spontaneous regression of the spontaneous melanomas has been observed to be as high as 96%. 23 …”

Porcine Melanotic Cutaneous Lesions and Lymph Nodes

“…10,37,50 The enzymes tyrosinase, a-mannosidase, and g-glutamyltransferase, which are involved in differentiation and spread of melanoma cells in humans, have also been demonstrated in melanoblastomabearing Libechov Minipig, and the activity of tyrosinase was considerably reduced in regressing melanomas. 5 In slaughter pigs, melanocytic tumors mainly occur in the Duroc and Duroc crossbreeds.…”

Type I collagen expression contributes to angiogenesis and the development of deeply invasive cutaneous melanoma

“…16 Similar to human melanoma, MeLiM melanoma invasion of the dermis can be classified according to Clark levels, although the relatively thin porcine papillary dermis does not allow a clear distinction between Clark level II and III. 16 Invasive melanoma growth correlates with increased blood vessel density, 17 but a causal relation has not been demonstrated. In this study, we have analyzed Col(I) expression in human and porcine melanoma, and attenuated its expression in the animal model by oral administration of halofuginone, a plant-derived alkaloid that inhibits transforming growth factor-b1 (TGFb1)-induced Col(I) mRNA transcription.…”

“…Melanoma development and early progression in Melanoblastoma-bearing Libechov Minipigs (MeLiM) closely resembles human melanoma progression with respect to skin architecture (comparable epidermal thickness and cellular architecture), epidermal localization of melanocytes and histopathology of the tumors. 16 Animals are born with or develop multiple highly pigmented melanocytic lesions within 6 weeks after birth and comprise intraepidermal atypical melanocytic proliferations (IAMPs), superficial spreading melanoma (SSM) and nodular melanoma (NM). 16 Similar to human melanoma, MeLiM melanoma invasion of the dermis can be classified according to Clark levels, although the relatively thin porcine papillary dermis does not allow a clear distinction between Clark level II and III.…”

“…16 Animals are born with or develop multiple highly pigmented melanocytic lesions within 6 weeks after birth and comprise intraepidermal atypical melanocytic proliferations (IAMPs), superficial spreading melanoma (SSM) and nodular melanoma (NM). 16 Similar to human melanoma, MeLiM melanoma invasion of the dermis can be classified according to Clark levels, although the relatively thin porcine papillary dermis does not allow a clear distinction between Clark level II and III. 16 Invasive melanoma growth correlates with increased blood vessel density, 17 but a causal relation has not been demonstrated.…”