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 immunocompromized 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 ~1,500mm3, 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.

中文翻译：

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骨肉瘤患者来源的异种移植物成功植入与临床病理学发现之间的关联。

虽然骨肉瘤是一种罕见疾病，全球发病率估计为 5.0/百万/年，但它是儿童和青少年中最常见的原发性骨肉瘤。在转化研究中，患者来源的异种移植 (PDX) 模型被认为是几种类型癌症的真实体内模型，因为肿瘤移植物忠实地保留了原发肿瘤的生物学特性。我们的目标是研究 PDX 形成与骨肉瘤患者的临床发现之间的关联，以及该模型在免疫功能低下的小鼠中保留亲本肿瘤特征的能力。从代表性活组织检查或手术切除获得的患者肿瘤的新鲜样品被植入裸鼠体内。当肿瘤生长达到~1,500mm3 时，将新鲜的 PDX 片段重新移植到新宿主中。在 40.54% 的植入样品中，在 19-225 天（中位数为 92 天）的潜伏期后获得了小鼠移植。我们证实了患者肿瘤与其各自建立的 PDX 之间的组织病理学保真度，包括生物标志物的表达。PDX 提取率在手术切除样本、化疗后手术样本和来自转移性疾病患者的样本中更高。总之，我们已经证明骨肉瘤 PDX 模型可靠地概括了小鼠连续传代后人类疾病的形态学方面。观察到更具侵袭性的骨肉瘤，包括那些出现转移性疾病的骨肉瘤，产生 PDX 的效率更高，这为解决临床肿瘤学中的几个悬而未决的问题提供了一个有希望的方案。