Top

Published in:

01-06-2009 | Original Paper

Expression of EAAT-1 distinguishes choroid plexus tumors from normal and reactive choroid plexus epithelium

Published in: Acta Neuropathologica | Issue 6/2009

Abstract

Microscopic distinction of normal choroid plexus (CP) from choroid plexus tumors (CPT) may be difficult, especially in small samples of well-differentiated CP papillomas. So far, there are no established markers that reliably distinguish normal and neoplastic CP epithelium. Recently, a correlation between expression/function of glial glutamate transporters EAAT-1 (GLAST) and EAAT-2 (Glt-1) and tumor proliferation has been reported. Furthermore, we previously found that CPTs frequently express EAAT-1, but not EAAT-2. We now compared expression of EAAT-1, EAAT-2 and GFAP in non-neoplastic CP (n = 68) and CPT (n = 79) by immunohistochemistry. Tissue of normal CP was obtained from 50 autopsy cases (20 normal and 30 pathologic brains) and 18 neurosurgical specimens that included 17 fetal, 21 pediatric and 30 adult cases. In non-neoplastic postnatal CP (n = 51), focal expression of EAAT-1 was found in only two pediatric cases (4%). In CPT, expression of EAAT-1 was found in 64 of 79 (81%) tumor samples and was significantly age-dependent (P < 0.0001). Hence, EAAT-1 expression distinguishes neoplastic from normal CP, both in children (P = 0.0032) and in adults (P < 0.0001). Immunostaining for EAAT-2 in selected samples from cases of different ages showed that normal CP (n = 15) or CPT (n = 16) lacked EAAT-2 expression. GFAP expression was found in 3 of 32 (10%) normal CP and in 28 of 73 (38%) tumor samples. In conclusion, in contrast to neoplastic CP samples, expression of EAAT-1 is exceptionally rare in non-neoplastic CP. Thus, EAAT-1 is superior to GFAP as a helpful diagnostic tool in CP samples.

Beschorner R, Dietz K, Schauer N et al (2007) Expression of EAAT1 reflects a possible neuroprotective function of reactive astrocytes and activated microglia following human traumatic brain injury. Histol Histopathol 22:515–526PubMed

Beschorner R, Pantazis G, Schittenhelm J, Meyermann R (2008) Membranous expression of EAAT-1 distinguishes neoplastic from normal choroid plexus epithelium. Acta Neuropathol 116:340

Beschorner R, Schittenhelm J, Schimmel H et al (2006) Choroid plexus tumors differ from metastatic carcinomas by expression of the excitatory amino acid transporter-1. Hum Pathol 37:854–860PubMedCrossRef

Beschorner R, Simon P, Schauer N et al (2007) Reactive astrocytes and activated microglial cells express EAAT1, but not EAAT2, reflecting a neuroprotective potential following ischaemia. Histopathol 50:897–910CrossRef

Bjornsen LP, Eid T, Holmseth S, Danbolt NC, Spencer DD, de Lanerolle NC (2007) Changes in glial glutamate transporters in human epileptogenic hippocampus: inadequate explanation for high extracellular glutamate during seizures. Neurobiol Dis 25:319–330PubMedCrossRef

Bonnin JM, Colon LE, Morawetz RB (1987) Focal glial differentiation and oncocytic transformation in choroid plexus papilloma. Acta Neuropathol 72:277–280PubMedCrossRef

Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254PubMedCrossRef

Catala M (1998) Embryonic and fetal development of structures associated with the cerebro-spinal fluid in man and other species Part I: the ventricular system, meninges and choroid plexuses. Arch Anat Cytol Pathol 46:153–169PubMed

Chretien F, Vallat-Decouvelaere AV, Bossuet C et al (2002) Expression of excitatory amino acid transporter-2 (EAAT-2) and glutamine synthetase (GS) in brain macrophages and microglia of SIVmac251-infected macaques. Neuropathol Appl Neurobiol 28:410–417PubMedCrossRef

10.

Ciceroni C, Arcella A, Mosillo P et al (2008) Type-3 metabotropic glutamate receptors negatively modulate bone morphogenetic protein receptor signaling and support the tumourigenic potential of glioma-initiating cells. Neuropharmacol 55:568–576CrossRef

11.

Duan S, Anderson CM, Stein BA, Swanson RA (1999) Glutamate induces rapid upregulation of astrocyte glutamate transport and cell-surface expression of GLAST. J Neurosci 19:10193–10200PubMed

12.

Dziegielewska KM, Evans CAN, New H, Reynolds ML, Saunders NR (1984) Synthesis of plasma proteins by rat fetal brain and choroid plexus. Int J Dev Neurosci 2:215–222CrossRef

13.

Figarella-Branger D, Lepidi H, Poncet C et al (1995) Differential expression of cell adhesion molecules (CAM), neural CAM and epithelial cadherin in ependymomas and choroid plexus tumors. Acta Neuropathol 89:248–257PubMedCrossRef

14.

Gandhi R, Luk KC, Rymar VV, Sadikot AF (2008) Group I mGluR5 metabotropic glutamate receptors regulate proliferation of neuronal progenitors in specific forebrain developmental domains. J Neurochem 104:155–172PubMed

15.

Gaudio RM, Tacconi L, Rossi ML (1998) Pathology of choroid plexus papillomas: a review. Clin Neurol Neurosurg 100:165–186PubMedCrossRef

16.

Hasselblatt M, Böhm C, Tatenhorst L et al (2006) Identification of novel diagnostic markers for choroid plexus tumors: a microarray-based approach. Am J Surg Pathol 30:66–74PubMedCrossRef

17.

Haugeto O, Ullensvang K, Levy LM et al (1996) Brain glutamate transporter proteins form homomultimers. J Biol Chem 271:27715–27722PubMedCrossRef

18.

Hurtado O, Moro MA, Cardenas A et al (2005) Neuroprotection afforded by prior citicoline administration in experimental brain ischemia: effects on glutamate transport. Neurobiol Dis 18:336–345PubMedCrossRef

19.

Jacobsen M, Jacobsen GK, Clausen PP, Saunders NR, Mollgard K (1982) Intracellular plasma proteins in human fetal choroid plexus during development. II. The distribution of prealbumin, albumin, alpha-fetoprotein, transferrin, IgG, IgA, IgM, and alpha 1-antitrypsin. Brain Res 255:251–262PubMed

20.

Jeibmann A, Hasselblatt M, Gerss J et al (2006) Prognostic implications of atypical histologic features in choroid plexus papilloma. J Neuropathol Exp Neurol 65:1069–1073PubMedCrossRef

21.

Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685PubMedCrossRef

22.

Lee SG, Su ZZ, Emdad L et al (2008) Mechanism of ceftriaxone induction of excitatory amino acid transporter-2 expression and glutamate uptake in primary human astrocytes. J Biol Chem 283:13116–13123PubMedCrossRef

23.

Longatti P, Basaldella L, Orvieto E, Dei TA, Martinuzzi A (2006) Aquaporin(s) expression in choroid plexus tumours. Pediatr Neurosurg 42:228–233PubMedCrossRef

24.

Lopez-Bayghen E, Ortega A (2004) Glutamate-dependent transcriptional regulation of GLAST: role of PKC. J Neurochem 91:200–209PubMedCrossRef

25.

Louis DN, Ohgaki H, Wiestler OD et al (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109PubMedCrossRef

26.

Luk KC, Kennedy TE, Sadikot AF (2003) Glutamate promotes proliferation of striatal neuronal progenitors by an NMDA receptor-mediated mechanism. J Neurosci 23:2239–2250PubMed

27.

Mori T, Tateishi N, Kagamiishi Y et al (2004) Attenuation of a delayed increase in the extracellular glutamate level in the peri-infarct area following focal cerebral ischemia by a novel agent ONO-2506. Neurochem Int 45:381–387PubMedCrossRef

28.

Nakamura Y, Becker LE, Marks A (1983) Distribution of immunoreactive S-100 protein in pediatric brain tumors. J Neuropathol Exp Neurol 42:136–145PubMedCrossRef

29.

Newcombe J, Uddin A, Dove R et al (2008) Glutamate receptor expression in multiple sclerosis lesions. Brain Pathol 18:52–61PubMedCrossRef

30.

Paulus W, Brandner S (2007) Choroid plexus tumours. In: Louis DN, Ohgaki H, Wiestler OD, Webster KC (eds) WHO classification of tumours of the central nervous system. IARC, Lyon, pp 81–86

31.

Redzic ZB, Preston JE, Duncan JA, Chodobski A, Szmydynger-Chodobska J (2005) The choroid plexus-cerebrospinal fluid system: from development to aging. Curr Top Dev Biol 71:1–52PubMedCrossRef

32.

Rothstein JD, Patel S, Regan MR et al (2005) Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature 433:73–77PubMedCrossRef

33.

Rozyczka J, Figiel M, Engele J (2004) Endothelins negatively regulate glial glutamate transporter expression. Brain Pathol 14:406–414PubMed

34.

Rzeski W, Ikonomidou C, Turski L (2002) Glutamate antagonists limit tumor growth. Biochem Pharmacol 64:1195–1200PubMedCrossRef

35.

Schmidt T, Landwehrmeyer GB, Schmitt I et al (1998) An isoform of ataxin-3 accumulates in the nucleus of neuronal cells in affected brain regions of SCA3 patients. Brain Pathol 8:669–679PubMedCrossRef

36.

Sheldon AL, Robinson MB (2007) The role of glutamate transporters in neurodegenerative diseases and potential opportunities for intervention. Neurochem Int 51:333–355PubMedCrossRef

37.

Shimada F, Shiga Y, Morikawa M et al (1999) The neuroprotective agent MS-153 stimulates glutamate uptake. Eur J Pharmacol 386:263–270PubMedCrossRef

38.

Sugiyama T, Sadzuka Y (1999) Combination of theanine with doxorubicin inhibits hepatic metastasis of M5076 ovarian sarcoma. Clin Cancer Res 5:413–416PubMed

39.

Sugiyama T, Sadzuka Y (2003) Theanine and glutamate transporter inhibitors enhance the antitumor efficacy of chemotherapeutic agents. Biochim Biophys Acta 1653:47–59PubMed

40.

Vanhoutte N, Hermans E (2008) Glutamate-induced glioma cell proliferation is prevented by functional expression of the glutamate transporter GLT-1. FEBS Lett 582:1847–1852PubMedCrossRef

41.

Varga Z, Vajtai I, Aguzzi A (1996) The standard isoform of CD44 is preferentially expressed in atypical papillomas and carcinomas of the choroid plexus. Pathol Res Pract 192:1225–1231PubMed

42.

Voutsinos-Porche B, Knott G, Tanaka K, Quairiaux C, Welker E, Bonvento G (2003) Glial glutamate transporters and maturation of the mouse somatosensory cortex. Cereb Cortex 13:1110–1121PubMedCrossRef

43.

Williams SM, Sullivan RK, Scott HL et al (2005) Glial glutamate transporter expression patterns in brains from multiple mammalian species. Glia 49:520–541PubMedCrossRef

Title: Expression of EAAT-1 distinguishes choroid plexus tumors from normal and reactive choroid plexus epithelium
Publication date: 01-06-2009
Published in: Acta Neuropathologica / Issue 6/2009
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-009-0519-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Expression of EAAT-1 distinguishes choroid plexus tumors from normal and reactive choroid plexus epithelium

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2009

APP/PS1KI bigenic mice develop early synaptic deficits and hippocampus atrophy

Staging/typing of Lewy body related α-synuclein pathology: a study of the BrainNet Europe Consortium

Purkinje cell axonal torpedoes are unrelated to advanced aging and likely reflect cerebellar injury

Histopathologic predictors of pilocytic astrocytoma event-free survival

Hippocampal sclerosis with four-repeat tau-positive round inclusions in the dentate gyrus: a new type of four-repeat tauopathy

Selective acquisition of IDH1 R132C mutations in astrocytomas associated with Li-Fraumeni syndrome