PATIENT-DERIVED XENOGRAFTS AS A PRECLINICAL MODEL FOR BONE SARCOMAS.

WALTER MEOHAS,ANNELIESE FORTUNA-COSTA,MARIA EUGENIA LEITE DUARTE,JOÃO ANTONIO MATHEUS GUIMARÃES,REGINA ALCANTARA GRANATO,RHAYRA BRAGA DIAS

doi:10.1590/1413-785220182602186998

Abstract

ABSTRACTObjective:The purpose of this study was to reproduce a mouse model of bone sarcomas for use in cancer research. Methods:A fresh sample of the tumor tissue was implanted subcutaneously into nude mice. When the patient-derived xenograft (PDX) reached a volume of 1500 mm3, it was harvested for re-implantation into additional mice. Histology was used to compare the morphological characteristics of different generations of sarcoma xenografts with the primary tumor. Results:Sixteen sarcoma tissue samples were engrafted into nude mice. Nine patients were diagnosed with osteosarcoma, two with chondrosarcoma, two with malignant peripheral nerve sheath tumor, one with synovial sarcoma, one with pleomorphic sarcoma, and one with Ewing’s sarcoma. PDX tumors were generated in 11 of the 16 implanted specimens (69% success rate in P1). Six P1 tumors grew sufficiently for transfer into additional mice, producing the P2 generation, and three P2 tumors established the P3 generation. Conclusion:PDX tumors generated from bone sarcomas were successfully established in immunodeficient mice and reproduced the characteristics of the primary tumor with a high degree of fidelity. The preclinical PDX model described herein may represent an important tool for translational oncology research and for evaluating therapeutic strategies for bone sarcomas. Level of Evidence I; Experimental study.

Highlights

Bone sarcomas are a heterogeneous group of rare highly malignant tumors of unknown origin that constitute 0.2% of all adult malignancies and 5% of malignant neoplasms of children and young people.[1]
Growth failure was considered in the absence of tumor growth four months after implantation. - Histopathological characterization of primary and patient-derived bone sarcoma xenograft (PDX) Fresh xenograft samples were fixed in 10% buffered formalin and paraffin-embedded blocks were prepared for all tumors
Eight patients were diagnosed with osteosarcoma, two with chondrosarcoma, two with malignant peripheral nerve sheath tumor (MPNST), one with synovial sarcoma, one with pleomorphic sarcoma and one with Ewing sarcoma

Summary

Introduction

Bone sarcomas are a heterogeneous group of rare highly malignant tumors of unknown origin that constitute 0.2% of all adult malignancies and 5% of malignant neoplasms of children and young people.[1] The clinical presentation of bone sarcomas is variable and nonspecific. The symptoms of pain, swelling and functional loss are restricted to the lesion region. The pain can be intermittent, persistent, and progressive with irradiation. Another characteristic of bone sarcomas is the rapid local volume increase associated with altered skin coloration plus. All authors declare no potential conflict of interest related to this article. Article received in 10/24/2017, approved in 11/06/2017

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