|
Development of new organoid model in patients with advanced biliary cancer.
|
|
Emiri Kita1,
Yoshitaka Hippo2,
Taketo Yamaguchi1 |
|
1Division of Gastroenterology, Chiba Cancer Center, 2Division of Molecular Carcinogenesis, Chiba Cancer Center Research Institute |
 |
|
| BACKGROUND AND AIM: Biliary cancer is well known for poor prognosis and majority of the cases are found inoperable at the initial diagnosis. Organoid culture is an emerging technique that enables propagation of primary cells in a physiological setting. The aim of this study was to establish methods of organoid culture from bile duct juice in patients with advanced biliary cancer. METHODS: Ninety five patients with biliary disease were enrolled. We conducted organoid culture from bile duct juice that were collected at therapeutic ERCP. As a reference, non-malignant cells were also subject to 3D-culture. Organoids were characterized in various aspects, including histology, immunochemistry, gene mutation and tumorigenesis in immunodeficient mice. RESULTS: Success rate for organoid culture from bile duct juice was as high as 89% (85/95cases). Histological studies revealed atypical cribriform structures in tumor-derived organoids, whereas only simple cystic structure could be observed for non-malignant organoids. KRAS mutation rate was 33% in tumor-derived organoids, consistent with reported mutation frequency in biliary tumors. Immunopositivity for p53 suggestive of its mutation was observed in 30%. About 40 % of organoids developed subcutaneous tumors in nude mice. CONCLUSION: Organoids recovered from bile duct juice well reflected the nature of underlying diseases, potentially contributing to development of companion diagnosis and novel therapeutics to biliary cancer. |
Index Term 1: 3D culture
Index Term 2: bile duct cancer
|
| Page Top |