Abstract 1464: Patient-derived tumor xenograft are susceptible to formation of B-cell lymphoma after initial transplantation of human carcinoma to immunodeficient mice

Abstract

Abstract Patient-derived xenograft (PDX) tumor models have emerged as new and effective models for developing novel anticancer therapies and personalized use of chemotherapeutic drugs. The PDX approach is based on the transplantation of primary or metastatic human tumors into highly immunodeficient NOD scid gamma (NSG) mice followed by continuous propagation of the established engrafment in mice. Clinicians can evaluate the effects of cancer drugs on their patients’ personalized tumor grafts enabling them to select the best treatment for the cancer patient. Here, we report that PDX tumors engrafted in NSG mice are susceptible to formation of B-cell lymphomas. We xenografted primary or metastatic human tumor fragments into NSG mice and found that tumors generated from patients’ samples of breast (1 out 3 cases), colon (2 out of 6 cases), pancreatic (1 out of 3 cases), bladder (1 out of 2 cases) and renal (1 out of 2 cases) cancer were histologically similar to lymphoid neoplasm. Moreover, we found that the first passage (F1) of some breast and pancreatic cancer PDX tumors could grow as a lymphoid neoplasm in one mouse and as an adenocarcinoma in another mouse after initial transplantation of the pieces from the same human tumor graft (F0). Whereas subcutaneous PDX tumors resembling primary human carcinoma histology were slow growing and non-metastatic, we found that subcutaneous PDX lymphoid neoplasms were fast growing and formed large metastatic lesions in lymph nodes, liver, lungs and spleen of the mouse. Immunohistochemical staining confirmed that lymphoma cells express human leucocyte common antigen CD45 and B-cell antigen CD19/20. By using Epstein-Barr Virus-encoded RNA (EBER) in situ hybridization, we found that PDX lymphoma cells were EBER-positive. Because B-cells are typically present in any solid malignant tumor, B-cell PDX lymphomas may evolve in a wide range of PDX tumor models. Our results suggest that histolopathological evaluation and lymphoid marker testing should be performed as part of the initial model characterization in order to exclude B-cell lymphomas during the development of PDX tumor model from solid human carcinoma. Citation Format: Gennadiy Bondarenko, Andrey Ugolkov, Piotr Kulesza, Stephen M. Rohan, Oleksii Dubrovskyi, Demirkan Gursel, Jeremy V. Mathews, Thomas V. O'Halloran, Jian-Jun Wei, Andrew P. Mazar. Patient-derived tumor xenograft are susceptible to formation of B-cell lymphoma after initial transplantation of human carcinoma to immunodeficient mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1464. doi:10.1158/1538-7445.AM2015-1464