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

Document Type : Original Article


1 Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2 Gene Therapy Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Pathology, Labbafinejad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

4 Department of Oncology, Shohada-e-Tajrish Medical Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

5 Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran


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 11 markers (Ki67, P63, GATA3, KRT5/6, KRT20, E-cadherin, 34βE12, PD-L1, EGFR, Nectin4, and HER2) were used to evaluate phenotype maintenance of original tumors.
Results: From 10 MIBC patients, two PDX models (P8X20 and P8X26) were successfully established (20% 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 7 markers for the model P8X20, and 8 markers for the model P8X26 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.


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