Artikel
Investigation of interaction between neuroepithelial brain tumours and surrounding brain parenchyma based on neural cell adhesion molecule: Loss of NCAM-140 expression with increase of malignancy enables identification of NCAM negative tumour border and invasion zone in human glioblastoma multiforme
Untersuchung der Interaktion zwischen neuroepithelialen Hirntumoren und dem umgebenden Hirngewebe auf der Basis des neuralen Zelladhäsionsmoleküls : Der Verlust der NCAM-140 Expression mit zunehmendem Malignitätsgrad ermöglicht die Identifikation der NCAM-negativen Tumorgrenze und der Invasionszone im humanen Glioblastoma multiforme
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Autoren
Veröffentlicht: | 4. Mai 2005 |
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Gliederung
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Objective
Human glioma cells massively invade surrounding brain parenchyma thereby interacting with their microenvironment. These complex glioma-brain-interactions may be one reason for aggressive glioma biology. In this study, we investigate the impact of neural cell adhesion molecule isoform 140 on glioma-brain-interaction in glioma invasion.
Methods
Immunohistochemistry was performed on consecutive sections of 38 human gliomas of astrocytic lineage with polyclonal antibodies to NCAM-140, CD31, and alpha-smooth muscle actin (ASMA). Morphology was characterised by hematoxylin/eosin staining. Autopsy material served as control. Densitometry was performed with Image 1.41 software for Mac computers. SPSS software version 12.0.2 was used for statistics.
Results
First, we found a down-regulation of NCAM-140 expression in human gliomas of astrocytic origin with increasing tumour grade according to WHO classification, as determined by microscopy. This was confirmed by densitometry. Mean density of NCAM-140 immunoreactivity was 173.6 (±3.15) in healthy brain tissue from autopsy series and was significantly different from all other glioma entities. Mean densities of 163.2 (±5.48) in low-grade astrocytoma and 162.4 (±6.44) in anaplastic astrocytoma were not significantly different from each other, but were different from mean density of NCAM-140 immunoreactivity in glioblastomas of 158.5 (±3.54) with statistical significance. Second, in 8 out of 11 glioblastomas, we could distinguish the NCAM-140 negative tumour border and/or tumour invasion zone from peritumoural tissue. Peritumoural parenchyma expressed high amounts of NCAM-140, whereas invading tumour cell nests of NCAM-140 negative glioblastomas were negative for NCAM-140 as well. Third, invasion pattern of glioblastomas varied extensively. Sharply demarcating tumour zones with invading tumour cell nests alternated with diffuse invasion areas, where single-cell-invasion occurred. CD31 and ASMA indicated arrangement of invading glioblastoma cells around neighbouring blood vessels.
Conclusions
The expression of NCAM-140 is inversely correlated to WHO grade in human astrocytic gliomas, with the glioblastomas demonstrating NCAM-140 negativity in most cases. Identification of tumour border and visualisation of invasion pattern in human glioblastomas is enabled by NCAM-140 negativity and has never been described before.