GENERATION AND PRELIMINARY CHARACTERIZATION OF PATIENT-DERIVED XENOGRAFTS OF ACRAL MELANOMA (AM-PDX)

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  • Presentation type: Especialização/Aperfeiçoamento
  • Track:
  • Keywords: Acral Melanoma; Patient-Derived Xenograft;
  • 1 Programa de Imunologia e Biologia de Tumores / Divisão de Pesquisa Experimental e Translacional / Instituto Nacional de Câncer
  • 2 UNIVERSIDAD NACIONAL AUTÓNOMA DE MÉXICO
  • 3 INSTITUTO NACIONAL DE CÂNCER (INCA)
  • 4 Instituto Nacional de Câncer (INCA)
  • 5 Instituto Nacional de Cancerología (INCan)
  • 6 Wellcome Sanger Institute
  • 7 Laboratorio Internacional de Investigación sobre el Genoma Humano

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Abstract

INTRODUCTION AND OBJECTIVE: Acral melanoma (AM) is a subtype of cutaneous melanoma that occurs on glabrous skin of the hands and feet (palms, soles and nail apparatus) and which is relatively more common in non-European descent populations such as those in Latin America. Compared to other subtypes, it is poorly studied and experimental models that faithfully reproduce human AM features are urgently needed. Here, we report the generation and preliminary characterization of a collection of patient-derived xenografts of acral melanomas (AM-PDX) from Latin-American patients. MATERIAL AND METHODS: Between March 2019 and February 2020, primary and metastatic samples of AM were collected from Brazilian and Mexican patients at the Instituto Nacional de Câncer (INCA) and the Instituto Nacional de Cancerologia (INCan), respectively. Samples were mechanically fragmented and subcutaneously implanted in NSG mice. Tumor growth was monitored weekly by calipering (length x width x height / 2). Patients’ clinical and histopathological data were collected from medical records. This study was approved by the Human and Animal Research Ethics Committees (CEP/CONEP and CEUA). RESULTS AND CONCLUSION: A total of 40 patients were included in the study, from whom 48 samples were collected. The mean age of the patients was 70.0 ± 2.09 years, 44% were female, and the majority were diagnosed with stage III disease. To date, twenty-six samples reached the experimental endpoint of either successful engraftment (n=15) or no tumor growth in six months (n=11), indicating a 58% success rate. The majority of the samples were acral lentiginous melanomas, ulcerated, with > 4mm Breslow depth and > 2 mitoses/mm2. There was no association between clinical and histopathological parameters and tumor growth in mice. Most lymph node metastases were successfully engrafted, but no differences were observed in the AM-PDX growth rate between the primary and metastatic samples. The implantation of the remaining samples of our collection and their molecular characterization are ongoing. This may reveal factors involved in successful establishment of AM-PDXs and also enable the investigation of the drivers and therapeutically targetable vulnerabilities of acral melanoma.

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Author

Mariana Pitombo

Boa tarde Jamila Machado, obrigada pela pergunta.  A taxa de sucesso de crescimento tumoral de acordo com o sítio anatômico atualmente é 50% para amostras plantares e 33,3% para amostras subungueal. Já em relação tumor primário versus metastático, a taxa de sucesso do tumor primário é  47% e metastático  87,5%, das amostras que tivemos PDX estabelecido atualmente.  Nossas amostras foram coletadas por cirurgia. 

Jamila Alessandra Perini Machado

Muito obrigada pelos esclarecimentos. Parabéns e sucesso com o trabalho!
Author

Mariana Pitombo

Olá, Anneliese, obrigada pela pergunta! Obrigada pelo elogio ao trabalho.  Os principais sítios anatômicos de metástase do melanoma acral são fígado e pulmão, órgãos estes que tiramos na eutanásia dos animais e mandamos para análise histopatológica para justamente investigar casos de metástase.  Sim, temos informações e acompanhamento desses pacientes através de prontuários médicos, e na nossa coorte hoje, o grupo sucesso de PDX (com pega) é composto majoritariamente pelo estágio avançado da doença.  Sim, acredito que com aumento da nossa taxa amostral essa diferença provavelmente possa dar estatística, baseado no gráfico B da figura 4 do meu pôster.  A avaliação dos parâmetros histológicos ainda está em andamento.        

Anneliese Fortuna de Azevedo Freire da Costa

Obrigada, Mariana! Siga em frente com o projeto! Estão de parabéns!!