umu.sePublikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Immunohistochemical analysis of LRIG proteins in meningiomas: correlation between estrogen receptor status and LRIG expression
Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
Department of Pathology, Center of Laboratory Medicine, Tampere University .
Department of Pathology, Center of Laboratory Medicine, Tampere University .
Department of Neurosurgery, Turku University Hospital, Turku, Finland.
Visa övriga samt affilieringar
2012 (Engelska)Ingår i: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 108, nr 3, s. 435-441Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The leucine-rich repeats and immunoglobulin-like domains (LRIG) protein family is comprised of three integral membrane proteins: LRIG1, LRIG2, and LRIG3. LRIG1 is a negative regulator of growth factor signaling. The expression and subcellular localization of LRIG proteins have prognostic implications in primary brain tumors, such as oligodendrogliomas and astrocytomas. The expression of LRIG proteins has not previously been studied in meningiomas. In this study, the expression of LRIG1, LRIG2, and LRIG3 was analyzed in 409 meningiomas by immunohistochemistry, and potential associations between LRIG protein expression and tumor grade, gender, progesterone receptor status, and estrogen receptor (ER) status were investigated. The LRIG proteins were most often expressed in the cytoplasm, though LRIG1 also showed prominent nuclear expression. Cytoplasmic expression of LRIG1 and LRIG2 correlated with histological subtypes of meningiomas (p = 0.038 and 0.013, respectively). Nuclear and cytoplasmic expression of LRIG1 was correlated with ER status (p = 0.003 and 0.004, respectively), as was cytoplasmic expression of LRIG2 (p = 0.006). This study is the first to examine the expression of LRIG proteins in meningiomas, and it shows a correlation between ER status and the expression of LRIG1 and LRIG2, which suggests a possible role for LRIG proteins in meningioma pathogenesis.

Ort, förlag, år, upplaga, sidor
2012. Vol. 108, nr 3, s. 435-441
Nyckelord [en]
Meningiomas, LRIG1, LRIG2, Estrogen receptor
Nationell ämneskategori
Cancer och onkologi
Forskningsämne
onkologi
Identifikatorer
URN: urn:nbn:se:umu:diva-79953DOI: 10.1007/s11060-012-0856-xOAI: oai:DiVA.org:umu-79953DiVA, id: diva2:645966
Tillgänglig från: 2013-09-06 Skapad: 2013-09-04 Senast uppdaterad: 2018-06-08Bibliografiskt granskad
Ingår i avhandling
1. Genotype-phenotype studies in brain tumors
Öppna denna publikation i ny flik eller fönster >>Genotype-phenotype studies in brain tumors
2013 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Meningioma and glioma are the most common primary brain tumors, but their etiologies are largely unknown. Although meningioma is usually benign, their intracranial location can lead to lethal consequences, and despite progress in surgery, radiotherapy, and chemotherapy the prognosis for patients with glioma remains poor. The only well-established environmental risk factor for meningioma and glioma is ionizing radiation. Evidence for inherited predisposition to meningioma and glioma is provided by a number of rare inherited syndromes where collectively these diseases account for only a small proportion of the twofold increased risk of brain tumors seen in first-degree relatives for meningioma and glioma patients. It is very possible that much of the excess familial risk is a consequence of co-inheritance of multiple low-risk genetic variations. With this in mind, the aims of the studies in this thesis were to discover genetic risk variants influencing the probability of acquiring the disease and to identify the association between risk variants on the tumor phenotype.

To identify genetic variants influencing meningioma risk, a comprehensive tagging of the selected genes in a case-control study was performed. We identified nine risk variants in

EGF, ERBB2, and LRIG2 genes. However, these findings could not be confirmed in another larger independent dataset. In addition, the study identified a correlation between LRIG2 protein expression and ER status when analyzed with different parameters. In a separate study with a larger sample of meningioma patients, the same correlation between LRIG2 and ER status was observed.

To explore the potential association between reported germline risk variants and somatic genetic events, matched tumor and blood samples from glioma patients were analyzed by SNP array. The results identified correlations between

EGFR gene variants and somatic aberrations within the EGFR locus and CDKN2A/B locus. To further study the relationship between germline risk variants and tumor phenotype, the same patient material was used and analyzed by three different techniques: SNP array, IHC, and FISH. The results revealed EGFR risk variants effecting copy number variation of the EGFR gene and the expression of the IDH1 and p53. Further comparison between different techniques such as SNP array and FISH analysis revealed the difficulty in achieving consistent results with different techniques.

To summarize, the glioma studies show a link between genotype and phenotype where genetic risk variants in the

EGFR gene were found to be associated with specific somatic aberrations. These associations are biologically interesting because EGFR is involved in multiple cellular processes. Additional studies of the direct functional role of these observations need to be conducted to elucidate the molecular mechanisms underlying the identified association between germline gene variants and somatic aberrations. For the meningioma studies, no significant risk variants influencing the disease were found but a correlation between LRIG2 and ER status was observed. This result suggests a potential role for the LRIG protein in the pathogenesis of meningioma, but more studies are needed to confirm this hypothesizes.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå Universitet, 2013. s. 64
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1657
Nyckelord
Glioma, Meningioma, SNP, IHC, FISH, LRIG2, EGF, EGFR, ERBB2, ER, CDKN2A/B, IDH1
Nationell ämneskategori
Cancer och onkologi
Forskningsämne
onkologi
Identifikatorer
urn:nbn:se:umu:diva-83185 (URN)978-91-7459-754-7 (ISBN)
Disputation
2013-12-12, Betula, by 6M, Norrlands universitetssjukhus, Umeå, 09:00 (Engelska)
Opponent
Handledare
Anmärkning

Cancer research foundation in northern Sweden and Lions cancer research foundation at Umeå university

Tillgänglig från: 2013-11-21 Skapad: 2013-11-20 Senast uppdaterad: 2018-06-08Bibliografiskt granskad

Open Access i DiVA

Ghasimi et al 2012(348 kB)384 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 348 kBChecksumma SHA-512
5f3f9a7bbeb0d8d9f496951c69e98c04a384c72a2af607ef17f6aacdb50d1eba87ecf7fd6c2fdc5676a36191dc8bde40a4faf659055f1bafaff26e22aa6edaf3
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltexthttp://urn:nbn:se:umu:diva-54238

Personposter BETA

Ghasimi, SomaBrännström, ThomasHedman, HåkanAndersson, Ulrika

Sök vidare i DiVA

Av författaren/redaktören
Ghasimi, SomaBrännström, ThomasHedman, HåkanAndersson, Ulrika
Av organisationen
Institutionen för strålningsvetenskaperInstitutionen för medicinsk biovetenskap
I samma tidskrift
Journal of Neuro-Oncology
Cancer och onkologi

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 384 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
urn-nbn

Altmetricpoäng

doi
urn-nbn
Totalt: 307 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf