Exp Clin Endocrinol Diabetes 2014; 122 - P021
DOI: 10.1055/s-0034-1372038

The driving force of craniopharyngioma growth

C Stache 1, A Hölsken 1, SM Schlaffer 2, A Hess 3, M Metzler 4, R Fahlbusch 5, J Flitsch 6, M Buchfelder 2, R Buslei 1
  • 1University Hospital Erlangen-Nuremberg, Department of Neuropathology, Erlangen, Germany
  • 2University Hospital Erlangen-Nuremberg, Department of Neurosurgery, Erlangen, Germany
  • 3University Erlangen-Nuremberg, Department of Pharmacology, Erlangen, Germany
  • 4University Hospital Erlangen-Nuremberg, Department of Pediatrics, Erlangen, Germany
  • 5International Neuroscience Institute, Hannover, Germany
  • 6University Hospital Hamburg-Eppendorf (UKE), Department of Neurosurgery, Hamburg, Germany

Objectives: Adamantinomatous craniopharyngiomas (adaCP) are benign, epithelial tumors of the sellar region, derogating the pituitary gland and the hypothalamus. Beside surgery and radiotherapy no chemotherapeutical treatment is approved. Recent in vitro studies identified promising substances to impede the migratory capacity of adaCP. A human intracranial adaCP mouse model is eligible in order to study and prove pathomechanisms of tumor progression.

Methods: Human primary adaCP tissue from three surgical specimens was stereotactically implanted into the brain of NMRInu/nu- (n = 14) or NSG-mice (n = 6). Control NMRInu/nu- mice (n = 6) received only PBS injections. Three months after tumor inoculation all mice were monitored by MR imaging (MRI). Subsequently brains were processed and microscopically reviewed using haematoxylin/eosin and immunohistochemical stainings.

Results: MRI and histology confirmed tumor engraftment in all 20 mice (100%) that obtained tumor transplants. The subdural lesions invaded subjacent brain tissue with finger-like protrusions and showed all histological hallmarks of human adaCP. Immunohistochemistry confirmed vital tumors (Mib-1) with distinct cytokeratin expression (KL1). Whole tumor reconstruction using serial sections identified whirl-like cell clusters with nuclear β-catenin accumulations being the driving force of adaCP outgrowth. These whirls were surrounded by a belt of CLDN1 expressing cells, showed activated EGFR, representing a target for drug therapy, and exhibited distinct CD133 positivity, suggesting the existence of a tumor stem cell niche in adaCP. No tumors were observed the control animals.

Conclusion: Orthotopic transplantation of human tumor tissue showed tumorigenic potential and generated vital tumors with histomorphological and immunohistochemical hallmarks of adaCP. This first intracranial mouse model of human CP provides the possibility to study tumor cell migration in vivo and to test novel treatment regimens.