Altered expression of beta-catenin/E-cadherin in meningiomas.
OBJECTIVE
Meningiomas are generally slow-growing benign tumours representing approximately 20% of all primary intracranial tumours. The hallmark of tumorigenesis of meningiomas is the loss of chromosome 22, including loss of heterozygosity of the neurofibromatosis type 2 (NF2) gene. The NF2 encoded protein merlin appears to function as a tumour suppressor gene by controlling cadherin-mediated cell-cell adhesion. The E-cadherin cell adhesion system includes beta-catenin that indirectly connects cadherin to actin filaments. The aim of this study was to analyse the expression and the subcellular location of E-cadherin and beta-catenin in human meningiomas, including meningiomas of different histomorphological subtypes and different World Health Organization (WHO) grades.


RESULTS
Immunohistochemical analysis revealed lack of E-cadherin expression at the cell membrane in 34% of meningiomas independent of their WHO grade. Loss of membranous beta-catenin occurred in 79% of meningiomas. An intense perinuclear granular immunoreactivity of beta-catenin without nuclear location was detected in the majority of meningiomas. Both immunofluorescence and Western blot analysis of fractionated meningioma cells located beta-catenin mostly on the Golgi apparatus and ER/Golgi intermediate compartment (ERGIC). Cytogenetic analysis of meningiomas showed no correlation between NF2 loss and the loss of the proper location of beta-catenin.


CONCLUSIONS
The lack of membranous beta-catenin and/or membranous E-cadherin in meningiomas may indicate an altered interaction between meningioma cells independent of loss of NF2 and independent of the tumour grade.
Brunner
E C
EC
Institute of Human Genetics, Medical School, University of Saarland, Homburg/Saar, Germany.
Romeike
B F M
BF
Jung
M
M
Comtesse
N
N
Meese
E
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000096:biosynthesis*; D002869:Chromosome Aberrations; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D020732:Cytogenetic Analysis; D005260:Female; D017353:Gene Deletion; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D007621:Karyotyping; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008579:Meningioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D025581:Neurofibromin 2 / Q000235:genetics; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000096:biosynthesis*
D015820:Cadherins; D025581:Neurofibromin 2; D051176:beta Catenin