Development and immunohistochemical characterization of patient-derived xenograft models for muscle invasive bladder cancer

Objective(s): Patient-derived xenograft (PDX) models have become a valuable tool to evaluate chemotherapeutics and investigate personalized cancer treatment options. The role of PDXs in the study of bladder cancer, especially for improvement of novel targeted therapies, continues to expand. In this study, we aimed to establish autochthonous PDX models of muscle-invasive bladder cancer (MIBC) to provide a useful tool to conduct research on personalized therapy. Materials and Methods: Tumors from MIBC patients undergoing radical cystectomy were subcutaneously transplanted into immunodeficient mice. The tumor size was measured by a caliper twice a week for up to five months. After the first growth in mice, they were serially passaged. Hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) of ۱۱ markers (Ki۶۷, P۶۳, GATA۳, KRT۵/۶, KRT۲۰, E-cadherin, ۳۴βE۱۲, PD-L۱, EGFR, Nectin۴, and HER۲) were used to evaluate phenotype maintenance of original tumors.Results: From ۱۰ MIBC patients, two PDX models (P۸X۲۰ and P۸X۲۶) were successfully established (۲۰% success rate). These models mostly retained primary tumor characteristics including histology, morphology, and molecular nature of the original cancer tissues. IHC analysis showed that the expression level of ۷ markers for the model P۸X۲۰, and ۸ markers for the model P۸X۲۶ was exactly similar between the patient tumor and the next generations.Conclusion: We developed the first autochthonous PDX models of MIBC in Iran. Our data suggested that the established MIBC PDX models reserved mostly histopathological characteristics of primary cancer and could provide a new tool to evaluate novel biomarkers, therapeutic targets, and drug combinations.

Keywords:

Animal model , chemotherapy , Muscle-invasive bladder cancer , Patient-derived xenograft , Targeted therapy