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

Pedro Duenisch, Rupert Reichart, Ulrike Mueller, Michael Brodhun, Rolf Bjerkvig, Bernd Romeike, Jan Walter, Christian Herbold, Christian R.A. Regenbrecht, Rolf Kalff, Susanne A. Kuhn

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)

Abstract

Purpose: 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. Materials and 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)399-414
Number of pages16
JournalJournal of Cancer Research and Clinical Oncology
Volume137
Issue number3
DOIs
Publication statusPublished - Mar 2011
Externally publishedYes

Keywords

  • Brain-tumor interface
  • Carcinoma brain metastases
  • Glioma
  • Meningioma
  • NCAM
  • WHO grade

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