精巣卵黄嚢腫瘍PDXモデルの確立と特性評価

To establish a patient-derived xenograft (PDX) model of testicular yolk sac tumor (TYST) that faithfully recapitulates the histopathological and molecular features of the primary tumor, thereby providing a robust pre-clinical platform for studying yolk sac tumor pathogenesis and evaluating novel therapeutics.

Patient-derived TYST tumor tissues were implanted subcutaneously in the right scapular region of immunodeficient mice (NPG and BALB/c nude strains) to generate a PDX model. Engrafted tumors were serially passaged and characterized by hematoxylin and eosin (H&E) staining, immunohistochemistry for AFP and SALL4, and PCR-based species identification to exclude murine lymphoma. The anti-tumor efficacy of the JEB regimen (carboplatin, etoposide, and bleomycin) was assessed using both in vivo experiments with the PDX model and ex vivo experiments utilizing the hydrogel-embedded histoculture drug sensitivity test (HDST).

The patient-derived TYST tumor tissues exhibited higher tumorigenicity in NPG and BALB/c nude mice, maintaining stability through serial passaging. H&E staining confirmed preservation of characteristic yolk sac morphology, including Schiller-Duval bodies. Immunohistochemical analysis demonstrated consistent expression of AFP and SALL4 in PDX tumors, mirroring the diagnostic profile of the original specimen. PCR results confirmed the human origin of the xenografts and ruled out spontaneous murine lymphomas. HDST assays revealed marked sensitivity to the JEB regimen, which was corroborated in vivo: JEB treatment induced significant tumor regression without causing clinically relevant body weight loss.

We successfully established a TYST PDX model that retains tissue structure and protein expression signature of the patient's tumor tissue. Furthermore, this PDX model demonstrates high sensitivity to standard JEB chemotherapy and represents a valuable resource for translational research in pediatric germ cell tumors.