An association between successful engraftment of osteosarcoma patient-derived xenografts and clinicopathological findings

• Anneliese Fortuna-Costa ^[4] ; Regina Alcantara Granato ^[1] ; Walter Meohas ^[5] ; Ana Cristina de Sá Lopes ^[5] ; Anabela Cunha Caruso ^[4] ; Rafael Castro e Silva Pinheiro ^[5] ; Pedro da Gama d'Eça ^[5] ; Rhayra Braga Dias ^[4] ; Jamila Alessandra Perini ^[4] ; Ana Paula Fernandes Barbosa ^[2] ; Renato Augusto Moreira de Sá ^[1] ; João Antonio Matheus Guimarães ^[4] ; Samuel S. Murray ^[3] ; Maria Eugenia Leite Duarte ^[3]
  1. [1] Universidade Federal Fluminense

     Universidade Federal Fluminense

     Brasil

     
  2. [2] Universidade Federal de Alagoas

     Universidade Federal de Alagoas

     Brasil

     
  3. [3] University of California System

     University of California System

     Estados Unidos

     
  4. [4] (INTO), Rio de Janeiro, RJ, Brazil
  5. [5] Traumatology (INTO), Rio de Janeiro, RJ, Brazil

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• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 35, Nº. 11, 2020, págs. 1295-1307
• Idioma: inglés
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  • . Although osteosarcoma is a rare disease, with a global incidence rate estimated at 5.0/million/ year, it is the most frequent primary bone sarcoma in children and adolescents. In translational research, the patient-derived xenograft (PDX) model is considered an authentic in vivo model for several types of cancer, as tumorgrafts faithfully retain the biological characteristics of the primary tumors. Our goal was to investigate the association between PDX formation and clinical findings of osteosarcoma patients and the ability of the model to preserve in immunocompromised mice the characteristics of the parental tumor. A fresh sample of the patient tumor obtained from a representative biopsy or from surgical resection was implanted into nude mice.

    When tumor outgrowths reached ~1,500 mm3, fresh PDX fragments were re-transplanted into new hosts.

    Engraftment in mice was obtained after a latency period of 19-225 days (median 92 days) in 40.54% of the implanted samples. We confirmed the histopathological fidelity between the patient tumor and their respective established PDXs, including the expression of biomarkers. PDX take rate was higher in surgical resection samples, in post-chemotherapy surgical samples and in samples from patients with metastatic disease at presentation. In conclusion, we have shown that the osteosarcoma PDX model reliably recapitulates the morphological aspects of the human disease after serial passage in mice. The observation that more aggressive forms of osteosarcoma, including those with metastatic disease at presentation, have a higher efficiency to generate PDXs provides a promising scenario to address several unanswered issues in clinical oncology.