title: Neural cell adhesion molecule isoform 140 declines with rise of WHO grade in human gliomas and serves as indicator for the invasion zone of multiform glioblastomas and brain metastases.
abstract: OBJECTIVE
  Gliomas are highly invasive neuroepithelial tumors with a propensity of malignant transformation and very restricted treatment options. The neural cell adhesion molecule (NCAM) modulates cellular migration, proliferation, and synaptic plasticity by homophilic and heterophilic interactions. Hereby, we investigated its relevance as a glioma tissue marker for the biological aggressiveness of these tumors and compared these features with the carcinoma brain metastasis invasion zone.
  
  
  METHODS
  We analyzed 194 human brain samples. Human tumor-free brain specimens served as control for the white and gray matter. In addition to that, we used human glioblastomas from nude rats. All tissues were investigated immunohistochemically for the expression of the NCAM isoform 140. Additionally, the multiplanar MRI-CT fusion neuronavigation-guided serial stereotactic biopsy was performed and completed by histopathological workup.
  
  
  RESULTS
  Human gliomas loose NCAM-140 with the rise of their WHO grade. Meningiomas are NCAM-140 negative. As the most striking feature, human brain metastases and the majority of human glioblastomas of our patients and of nude rats were totally NCAM-140 negative. This NCAM negativity led us to the conclusion of three different main glioblastoma invasion patterns. Surprisingly, the majority of brain metastasis samples that contained surrounding brain parenchyma demonstrated invasive tumor cell nests beyond the sharply demarcated metastasis border. We also found invasive metastatic cell nests outside the contrast enhancing tumor zone by means of the MRI-CT fusion neuronavigation-guided serial stereotactic biopsy.
  
  
  CONCLUSIONS
  The expression of NCAM-140 inversely correlates with the WHO grade of human gliomas. The lost expression of NCAM-140 in human glioblastomas and in brain metastases enables the investigation of the brain-tumor interface and the definition of glioblastoma invasion patterns and shows that brain metastases are more invasive than ever thought.
authors.affiliation: Department of Neurosurgery, Medical Center, Friedrich-Schiller-University, Erlanger Allee 101, 07747, Jena, Germany.
authors.forename: Pedro
authors.initials: P
authors.lastname: Duenisch
authors.forename: Rupert
authors.initials: R
authors.lastname: Reichart
authors.forename: Ulrike
authors.initials: U
authors.lastname: Mueller
authors.forename: Michael
authors.initials: M
authors.lastname: Brodhun
authors.forename: Rolf
authors.initials: R
authors.lastname: Bjerkvig
authors.forename: Bernd
authors.initials: B
authors.lastname: Romeike
authors.forename: Jan
authors.initials: J
authors.lastname: Walter
authors.forename: Christian
authors.initials: C
authors.lastname: Herbold
authors.forename: Christian R A
authors.initials: CR
authors.lastname: Regenbrecht
authors.forename: Rolf
authors.initials: R
authors.lastname: Kalff
authors.forename: Susanne A
authors.initials: SA
authors.lastname: Kuhn
mesh_terms: D000818:Animals; D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001706:Biopsy / Q000379:methods; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis*; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008579:Meningioma / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D009361:Neoplasm Invasiveness; D051381:Rats; D011923:Rats, Nude
chemical_list: D014408:Biomarkers, Tumor; D015816:Cell Adhesion Molecules, Neuronal; C520249:NCAM140, human