Publication: Notch receptors in human choroid plexus tumors
Authors
Beschorner, R. ; Waidelich, J. ; Trautmann, K. ; Psaras, T. ; Schittenhelm, J.
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Publisher
F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Notch signaling plays a role in development
and formation of the normal choroid plexus (nCP), and
in formation of various tumors in humans. Activation of
Notch3 has been reported to promote tumor growth in
invasive gliomas and to initiate formation of choroid
plexus tumors (CPT) in mice.
We investigated the expression of all currently
known Notch receptors (Notch 1-4) in 55 samples of
nCP and 88 CPT, including 61 choroid plexus
papillomas (CPP), 22 atypical CPP and 5 choroid plexus
carcinomas by immunohistochemistry. Notch expression
was semiquantitatively evaluated separately for
membranous/cytoplasmic and for nuclear staining. In
addition, we examined Her2 expression (EGFR2,
Her2/neu, ErbB2, CD340) because of its functional link
to Notch signaling.
All samples were negative for Notch3.
Membranous/cytoplasmic expression of Notch1
(p<0.0001) and Notch4 (p=0.046) was significantly
higher, whereas Notch2 expression was significantly
lower (p<0.0001) in nCP compared to CPT. Nuclear
expression of Notch1, -2 and -4 was significantly higher
in CPT compared to nCP (p<0.0001 each). Expression of
Notch2 and Notch4 showed a shift from a prevailing
membranous/cytoplasmic expression in nCP to a
predominant nuclear expression in CPT. Her2 was
weakly expressed in 42/84 CPT but only in 2/53 nCP
(p=0.0001) and positively correlated with nuclear
expression of Notch1, -2 and 4 in CPT.
In summary, a shift between membranous/cytoplasmic
(non-canonical signaling pathway) and nuclear
expression (canonical signaling pathway) of Notch1, -2
and -4 and upregulation of Her2 indicate neoplastic
transformation in human CP and may reveal new
therapeutic approaches.
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Citation
Histology and Histopathology, vol. 28, nº 8 (2013)
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