PRELIMINARY CHARACTERIZATION OF SPONTANEOUS METASTASES IN A PATIENT-DERIVED XENOGRAFTS OF ACRAL MELANOMA

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  • Presentation type: ES - Especialização/Aperfeiçoamento
  • Track:
  • Keywords: Acral Melanoma; Patient-Derived Xenograft; metastases;
  • 1 Programa de Imunologia e Biologia de Tumores, Instituto Nacional de Câncer
  • 2 Centro das Ciências Biológicas e da Saúde, Universidade Federal do Oeste da Bahia
  • 3 Seção de tecido ósseo e conectivo, Instituto Nacional de Câncer
  • 4 Divisão de Patologia, Instituto Nacional de Câncer
  • 5 Divisão de Pesquisa Clínica e Desenvolvimento Tecnológico, Instituto Nacional de Câncer
  • 6 Departamento de Patologia Geral, Universidade Federal de Minas Gerais

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Abstract

INTRODUCTION AND OBJECTIVES: Melanomas are highly aggressive mainly because of their high capacity to metastasize. This scenario is also seen, more alarmingly, in acral melanomas (AM), a poorly studied cutaneous melanoma subtype with fewer therapeutic strategies available. Thus, experimental models that faithfully reproduce the characteristics of human AM progression are urgently needed. Here, we report the preliminary characterization of spontaneous metastases in a collection of xenografts derived from acral melanoma patients (AM-PDX). MATERIAL AND METHODS: Hematoxylin & Eosin (HE)-stained slides representative of all organs collected from AM-PDX-bearing mice were analysed using a brightfield microscope. The suspected presence of human tumour cells in murine organs was further analyzed by immunohistochemical staining of the human cell-specific marker Lamin A/C (M00438, Boster Bio), and the melanoma-specific cell markers Melan A (ab51061, Abcam) and HMB45 (790-4366, Roche). Spread of human tumour cells to murine organs was classified as metastases (>0.2 mm in the greatest extent), and isolated tumour cells (<0.2 mm). PDX Latency time (time for subcutaneous tumours to reach 200 mm3) was calculated as a measure of successful engraftment for all the positive cases. Disease progression and metastatic disease was accessed from the electronic medical records of each patient. This study was approved by the Human and Animal Research Ethics Committees (CEP/CONEP and CEUA). RESULTS AND CONCLUSION: Out of the 49 experimental groups implanted with human AM samples to date, 42% (n=21) reached the experimental endpoint of successful engraftment. Of those, 19 were analyzed and confirmation of metastases and/or isolated tumour cells occurred in 47% (n=9). The groups with no subcutaneous engraftment were also analyzed, but no evidence of metastases and/or isolated tumour cells was observed. The main organs affected by metastases were lung (40%) and liver (40%), but some cases had other anatomic locations affected such as kidney and lymph nodes. In the case of isolated tumour cells, 96% were detected in lungs and 4% in livers. To investigate whether subcutaneous tumour growth time affected tumour cell spread to distant organs, we compared the PDX latency time of the mice with confirmed metastases with the mice with confirmed isolated tumour cell nests, but no difference was observed. To date, we conclude that AM-PDXs can spontaneously spread to distant organs where they form either metastatic nodules or isolated tumour cell nests. The expansion of the AM-PDX collection will allow us to study critical aspects in tumour progression and metastases formation in acral melanoma.

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