Establishment of patient-derived subrenal capsule xenograft of pancreatic cancers in NOD/SCID mice: potential models for drug responses of personalized chemotherapy (#204)
Objective: To establish and evaluate the patient-derived subrenal capsule (SRC) xenografts in nonobese diabetic/severe combined immunodeficient mice (NOD/SCID) mice as a novel pre-clinical model for predicting chemotherapeutic responses in pancreatic ductal adenocarcinoma (PDAC).
Methods: Pieces of PDAC tumour resected from 13 patients were grafted under the renal capsules in NOD/SCID mice. Following 4 weeks engraftment, the mice randomly received either Gemcitabine or saline (control) treatment. After 8 weeks, the tumour grafts were harvested and compared with the original tumour tissues. Gemcitabine responses were determined by: 1) the mean post-graft area (mm2) of Gemcitabine vs control groups; 2) the histologic morphology; 3) the immunohistochemical (IHC) scores of a variety of markers; and 4) correlation with clinical outcome.
Results: Xenografts from 13 PDAC tumours were successfully established with a 91.57% of engraftment rate. Comparisons between the original and post-graft tissues demonstrated similar histopathological and immunostaining features (>90% of concordance). Moreover, of the 13 patients, two developed early metastasis and both of these were unresponsive to Gemcitabine in the SRC xenograft mice. Three patients, whose tumours responded to Gemcitabine treatment as measured by a reduction in tumour volume (P < 0.05) and a decrease of the expressions of CK7, CK20 and Ki-67 compared to the control mice, have not developed recurrence during the study period.
Conclusion: The SRC xenografts of the patient-derived pancreatic cancers in NOD/SCID mice can retain major histopathological and immunohistochemical characteristics of the original tumour. The high engraftment rate allows the use of such xenografts as a potential tool to assess an individual patient response to Gemcitabine treatment within 8 weeks after pancreatic tumour resection.
Acknowledgement: This study was supported by Cancer Surgery Research Foundation, Ramsay Surgical Grant and RNSH Flower & Gift Shop Grant.