Histopathologic and immunophenotypic characterization of patient-derived pediatric malignant hepatocellular tumor xenografts (PDXs).
Pathol Res Pract
; 255: 155163, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38394806
ABSTRACT
Advances in targeted therapies for pediatric hepatocellular tumors have been limited due to a paucity of clinically relevant models. Establishment and validation of intrahepatic patient-derived xenograft (PDX) models would help bridging this gap. The aim of this study is to compare the histomorphologic and immunophenotypic fidelity of patient tumors and their corresponding intrahepatic PDX models. Murine PDX models were established by intrahepatic implantation of patient tumors. Pathology slides from both patients and their corresponding PDX models were reviewed and quantitatively assessed for various histologic components and immunophenotypic markers. Ten PDX models were successfully established from nine patients with pre- (n=3) and post- (n=6) chemotherapy samples; diagnosed of hepatoblastoma (n=8) and hepatocellular neoplasm, not otherwise specified (n=1). Two of nine (22.2%) patients showed ≥75% fetal component; however, the corresponding PDX models did not maintain this fetal differentiation. High grade histology was seen in three patients (33.3%) and overrepresented in six PDX models (60%). Within the subset of three PDXs that were further characterized, significant IHC concordance was seen in all 3 models for CK7, CK19, Ki-67, and p53; and 2 of 3 models for Sox9 and Beta-catenin. GPC-3 and GS showed variable to moderate concordance, while Hepar was the least concordant. Our study shows that in general, the PDX models appear to represent the higher-grade component of the original tumor and show significant concordance for Ki-67, making them appropriate tools for testing new therapies for the most aggressive, therapy-resistant tumors.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
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Neoplasias Hepáticas
Limite:
Animals
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Child
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article