Endocrine Abstracts

Only two human cell lines are available for adrenocortical carcinoma (ACC) which do not reflect the functional heterogeneity of individual patient tumors and metastases. To overcome the lack of preclinical models for testing of novel therapeutic options in recent years we aimed at the development of patient-individual tumor models for endocrine tumors. Therefore, pieces of surgically excised patient tumors were implanted subcutaneously in the neck of athymic nude mice. To investigate whether morphological and functional characteristics between tumor samples after mouse engraftment in comparison to the original tumor would be comparable, we examined vitality, proliferation, vascularization and endocrine markers of the explanted material and the original patient tumor. During these studies one xenograft (MUC-1), derived from a neck metastasis of an ACC, showed extraordinary engraftment properties and sustained tumor growth over several passages in the murine host. Immunohistochemical analysis of explanted tumors revealed highly vascularized tissues of SF-1 positive cells with Ki67 indices of 37.7±0.8%. Transplanted mice had measurable cortisol levels of 2.7 μg/dl suggesting persistent glucocorticoid production by tumor cells. During ongoing studies we were able to utilize MUC-1 tumor bearing mice as an in vivo model in addition to the classical NCIh295-xenografts to investigate putative practicability in preclinical therapeutic settings. In an attempt to furthermore allow in vitroapplications we established a primary culture based on explanted xenograft pieces which shows upon several passages promising proliferative characteristics with a Ki67 index of 38.6±3.2% and sustained SF-1-expression. In ongoing experiments we are currently aiming at the overall characterization of MUC-1 to potentially provide a third preclinical tumor model for ACCs.