TMOD-06. ESTABLISHMENT OF PITUITARY NEUROENDOCRINE TUMOR (PITNET) ORGANOID MODELS

Abstract Pituitary neuroendocrine tumors (PitNETs) are tumors that originate from the anterior pituitary gland. While they are mostly benign, they can cause various clinical symptoms due to hormonal secretion abnormalities. PitNET can be broadly categorized into three lineages, each of which has its differentiation controlled by specific transcription factors. Treatment options for PitNET include surgical resection and pharmacotherapy, but available drugs are limited, and their efficacy markers remain unclear. To develop novel drugs for PitNET and identify their efficacy markers, it is necessary to develop new research models. In recent years, organoid models have garnered attention as novel research models for various cancer types. In this study, we established novel organoid models derived from PitNET patients and analyzed their histological and endocrinological characteristics. Surgical specimens from 4 cases of somatotroph adenoma, 1 case of double adenoma, 1 case of gonadotroph adenoma, and 1 case of corticotroph adenoma were minced in dissection medium and embedded in Matrigel basement membrane matrix respectively. The organoids were cultured under 5% CO2 at 37°C using media supplemented with various growth factors. After 28 days of culture, formalin-fixed paraffin-embedded sections were prepared to examine histological homology with patient tumors. Hematoxylin and eosin staining results showed that all organoids maintained cell morphology and tissue structure similar to the original tumors. Immunohistochemical staining for markers specific to each PitNET revealed similar staining patterns between the organoids and the original tumors. Furthermore, analysis of hormone levels in the culture medium showed that hormone production capabilities, such as growth hormone and follicle stimulating hormone, were maintained even after long-term culture. In this study, we successfully established PitNET organoid models that retain histological and endocrinological characteristics. These models are expected to serve as useful research tools for elucidating the molecular mechanisms of PitNET and developing novel therapies targeting critical molecular abnormalities.