Successful application of endoscopic ultrasound-guided fine needle biopsy to establish pancreatic patient-derived tumor xenografts: a pilot study.
Background and study aim:Typically, pancreatic patient-derived tumor xenografts (PDXs) are established by transplanting large tumor biopsies obtained through invasive surgery approaches into immunocompromised mice. We aimed to develop pancreatic PDXs by transplanting tumor tissue acquired by endoscopic ultrasound (EUS)-guided fine needle biopsies (FNB), assess take rates compared to surgery-derived PDXs, and demonstrate the histological and genetic resemblance to the original tumor.Patients and methods:Biopsies of untreated pancreatic carcinoma were collected at surgery and during EUS and processed to generate PDXs.Results:By centrifugation of FNB-derived tissue prior to engraftment, we achieved an engraftment rate of 60 % (6/10). Despite a decrease in stromal tissue, the general morphology of FNB-derived PDXs was conserved as assessed by histopathology. At the genetic level, somatic mutation and copy number profiles were largely similar to the primary tumor.Conclusion:We show that it is technically feasible to establish pancreatic PDXs using a minimally invasive sampling technique, such as EUS-FNB. Although only a limited amount of tumor tissue was acquired, we obtained results similar to those from surgery-derived PDXs.
Laboratory of Gynecologic Oncology, Department of Oncology, University of Leuven, Leuven, Belgium.
Els
E
Hermans
Department of Gastroenterology and Hepatology, University of Leuven, Leuven, Belgium.
Schalk W
SW
Van der Merwe
Laboratory of Gynecologic Oncology, Department of Oncology, University of Leuven, Leuven, Belgium.
Jeroen
J
Depreeuw
Department of Gastroenterology and Hepatology, University of Leuven, Leuven, Belgium.
Jeroen
J
Dekervel
Center for the Biology of Disease, KU Leuven Center for Human Genetics - InfraMouse, VIB, University of Leuven, Leuven, Belgium.
Enrico
E
Radaelli
Division of Translational Cell & Tissue Research, Department of Imaging and Pathology, University of Leuven, Leuven, Belgium.
Tania
T
Roskams
Department of Gastroenterology and Hepatology, University of Leuven, Leuven, Belgium.
Jos
J
van Pelt Jos
Department of Abdominal Surgery, University of Leuven, Leuven, Belgium.
Baki
B
Topal
Department of Gastroenterology and Hepatology, University of Leuven, Leuven, Belgium.
Chris
C
Verslype
Department of Gastroenterology and Hepatology, University of Leuven, Leuven, Belgium.
Hans
H
Prenen
Department of Gastroenterology and Hepatology, University of Leuven, Leuven, Belgium.
Werner
W
Van Steenbergen
Department of Gastroenterology and Hepatology, University of Leuven, Leuven, Belgium.
Frederik
F
Nevens
Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Leuven, Belgium.
Diether
D
Lambrechts
Laboratory of Gynecologic Oncology, Department of Oncology, University of Leuven, Leuven, Belgium.
Frédéric
F
Amant
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology*; D004252:DNA Mutational Analysis; D061765:Endoscopic Ultrasound-Guided Fine Needle Aspiration; D059472:Exome; D005260:Female; D018628:Gene Dosage; D006085:Graft Survival; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009154:Mutation; D009368:Neoplasm Transplantation / Q000379:methods* / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D010865:Pilot Projects; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
C117307:KRAS protein, human; D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras)