Modeling of Patient-Derived 3D Organoids of Thyroid Cancer: From Cells to Care
Nam Kyung Kim1, So Jeong Lee1, Junu Kim1
1Department of Surgery, Thyroid Cancer Center, Gangnam Severance Hospital, Institute of Refractory Thyroid Cancer, Yonsei University College of Medicine, Seoul, South Korea, yonsei.ac.kr.
Introduction:
Three-dimensional (3D) organoids derived from patient tissues have emerged as promising preclinical models that preserve tumor architecture and phenotypic heterogeneity better than conventional two-dimensional cultures. This study aimed to establish patient-derived 3D organoid models for anaplastic thyroid carcinoma (ATC) and clinically radioiodine-refractory papillary thyroid carcinoma (RAIR-PTC) and evaluate whether they retained the histopathologic and immunophenotypic features of their source tumors.
Methods:
Tumor tissues from patients with ATC and RAIR-PTC were collected, dissociated, and embedded in Matrigel for 3D culture. Organoid growth was monitored during serial passaging. Histopathologic, immunophenotypic, and targeted molecular analyses were performed.
Results:
The TCO001 sample, derived from ATC, showed substantial growth for more than five months, up to Passage 11, whereas the TCO002 sample, derived from RAIR-PTC, exhibited limited proliferation and could not be maintained beyond Passage 3 after four months. These differences in culture performance were further supported by Ki-67 and p53 staining, which demonstrated markedly higher proliferative activity and a more aberrant p53 expression pattern in TCO001 than in TCO002. Histopathologic and immunophenotypic analyses showed a dedifferentiated, ATC-like phenotype in TCO001 and a more differentiated thyroid carcinoma-like phenotype in TCO002. Targeted molecular analysis further supported the biological differences between the two lines: TCO001 harbored a BRAF mutation and a TERT promoter alteration, whereas TCO002 was wild type for both genes, consistent with the matched primary tumor tissue.
Discussion:
This study provides preliminary proof of concept that patient-derived organoid technology can be extended to aggressive thyroid cancer phenotypes and preserve subtype-relevant differences in differentiation state. Although preliminary, these findings support the value of thyroid cancer organoids as patient-relevant preclinical models and provide a basis for future molecular, functional, and therapeutic studies in aggressive thyroid cancer.
