In an attempt to amend the lack of preclinical models for endocrine tumors, we recently initiated establishment of patient-individual tumor models. Pieces from four adrenocortical carcinomas (ACC), one aldosterone producing adenoma (APA), one pheochromocytoma (pheo), one metastasis of a malignant pheo, one pheo and medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2 and 11 neuroendocrine tumors (NETs, nine NETs of the gastroenteropancreatic system including three metastasis as well as one primary tumor and one metastasis of Merkel cell carcinoma) were implanted subcutaneously into immunodeficient mice. CD31 analyses after tumor explantation revealed heterogeneous grades of vascularization for ACCs and NETs (from high to absent) which seemed to be overall not dependent on tumor origin. Single explants (E) showed often ki67 indices (%) and SF-1 (positive cells/six high power fields) or chromogranin A stainings (ChrA morphology and stained area as % of total) comparable (P>0.05) to the original patient tumor (ACC1 ki67, patient: 7.9±2.3, E: 8.9±2; SF-1, patient: 4.2±0.7, E: 4.2±0.6; NET1 ki67, patient: 7.3±1.4, E: 7.7±1.1; ChrA, patient and E: 3060%, nest-shaped). However, various explants revealed intra-tumoral heterogeneities maybe reflecting different regions within one patients tumor (ACC2 ki67, patient: 9.7±2.6 vs E1: 2.8±0.9, P<0.05; E2: 2±1.2, P<0.05; E3: 11.3±3.3, P>0.05; SF-1, patient: 3.3±0.4 vs E1: 3.2±0.4, P>0.05; E2: 0.5±0.1, P<0.0001; E3: 1.1±0.2, P<0.0001; NET2 ki67, patient: 2±1 vs E1: 10.3±0.7, P<0.0001; E2: 7.1±0.9, P<0.001; E3: 13.1±1.9, P<0.0001; E4: 2.7±0.6, P>0.05; ChrA, patient: nest-shaped 60±7.1, E1: nest-shaped 21.9±3.5; E2: 8.8±7, nest-shaped; E3: 0±4.2, diffuse; E4: 10±3, diffuse). APA and pheos were low or not vascularized and ki67 indices were comparable with patient tumors (pheo, patient: 2.9±0.4, E1: 2.9±0.7, E2: 2.5±0.6; APA, patient: 3.2±0.9, E1:1.6±0.5, E2: 3.6±1.7). During ongoing preclinical studies we plan to include groups with patient-tumor bearing mice to investigate putative applicability in therapeutic settings.
27 Apr - 01 May 2013
European Society of Endocrinology