Skip to main content

Advertisement

Log in

Immunohistochemical analysis of LRIG proteins in meningiomas: correlation between estrogen receptor status and LRIG expression

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Wiemels J, Wrensch M, Claus EB (2010) Epidemiology and etiology of meningioma. J Neurooncol 99(3):307–314

    Article  PubMed  Google Scholar 

  2. Patil CG et al (2010) Craniotomy for resection of meningioma in the elderly: a multicentre, prospective analysis from the National Surgical Quality Improvement Program. J Neurol Neurosurg Psychiatry 81(5):502–505

    Article  PubMed  Google Scholar 

  3. Malmer B, Henriksson R, Gronberg H (2003) Familial brain tumours—genetics or environment? A nationwide cohort study of cancer risk in spouses and first-degree relatives of brain tumour patients. Int J Cancer 106(2):260–263

    Article  PubMed  CAS  Google Scholar 

  4. Preston DL et al (2002) Tumors of the nervous system and pituitary gland associated with atomic bomb radiation exposure. J Natl Cancer Inst 94(20):1555–1563

    Article  PubMed  CAS  Google Scholar 

  5. Umansky F et al (2008) Radiation-induced meningioma. Neurosurg Focus 24(5):E7

    Article  PubMed  Google Scholar 

  6. Sadetzki S et al (2005) Genotyping of patients with sporadic and radiation-associated meningiomas. Cancer Epidemiol Biomarkers Prev 14(4):969–976

    Article  PubMed  CAS  Google Scholar 

  7. Sadetzki S et al (2002) Radiation-induced meningioma: a descriptive study of 253 cases. J Neurosurg 97(5):1078–1082

    Article  PubMed  Google Scholar 

  8. Schoenberg BS, Christine BW, Whisnant JP (1975) Nervous system neoplasms and primary malignancies of other sites. The unique association between meningiomas and breast cancer. Neurology 25(8):705–712

    Article  PubMed  CAS  Google Scholar 

  9. Custer B et al (2006) Hormonal exposures and the risk of intracranial meningioma in women: a population-based case–control study. BMC Cancer 6:152

    Article  PubMed  Google Scholar 

  10. Guo D et al (2004) The LRIG gene family has three vertebrate paralogs widely expressed in human and mouse tissues and a homolog in Ascidiacea. Genomics 84(1):157–165

    Article  PubMed  CAS  Google Scholar 

  11. Holmlund C et al (2004) Characterization and tissue-specific expression of human LRIG2. Gene 332:35–43

    Article  PubMed  CAS  Google Scholar 

  12. Nilsson J et al (2001) Cloning, characterization, and expression of human LIG1. Biochem Biophys Res Commun 284(5):1155–1161

    Article  PubMed  CAS  Google Scholar 

  13. Hedman H, Henriksson R (2007) LRIG inhibitors of growth factor signalling—double-edged swords in human cancer? Eur J Cancer 43(4):676–682

    Article  PubMed  CAS  Google Scholar 

  14. Karlsson T et al (2008) Redistribution of LRIG proteins in psoriasis. J Invest Dermatol 128(5):1192–1195

    Article  PubMed  CAS  Google Scholar 

  15. Gur G et al (2004) LRIG1 restricts growth factor signaling by enhancing receptor ubiquitylation and degradation. EMBO J 23(16):3270–3281

    Article  PubMed  CAS  Google Scholar 

  16. Laederich MB et al (2004) The leucine-rich repeat protein LRIG1 is a negative regulator of ErbB family receptor tyrosine kinases. J Biol Chem 279(45):47050–47056

    Article  PubMed  CAS  Google Scholar 

  17. Yi W et al (2011) Paracrine regulation of growth factor signaling by shed leucine-rich repeats and immunoglobulin-like domains 1. Exp Cell Res 317(4):504–512

    Article  PubMed  CAS  Google Scholar 

  18. Torp SH et al (1992) Expression of epidermal growth factor receptor in human meningiomas and meningeal tissue. APMIS 100(9):797–802

    Article  PubMed  CAS  Google Scholar 

  19. Andersson U et al (2004) Epidermal growth factor receptor family (EGFR, ErbB2-4) in gliomas and meningiomas. Acta Neuropathol 108(2):135–142

    Article  PubMed  CAS  Google Scholar 

  20. Wernicke AG et al (2010) Assessment of epidermal growth factor receptor (EGFR) expression in human meningioma. Radiat Oncol 5:46. doi:10.1186/1748-717X-5-46

    Article  PubMed  Google Scholar 

  21. Hedman H et al (2010) LRIG2 in contrast to LRIG1 predicts poor survival in early-stage squamous cell carcinoma of the uterine cervix. Acta Oncol 49(6):812–815

    Article  PubMed  Google Scholar 

  22. Krig SR et al (2011) Lrig1 is an estrogen-regulated growth suppressor and correlates with longer relapse-free survival in ER{alpha}-positive breast cancer. Mol Cancer Res 9(10):1406–1417

    Article  PubMed  CAS  Google Scholar 

  23. Tanemura A et al (2005) LRIG-1 provides a novel prognostic predictor in squamous cell carcinoma of the skin: immunohistochemical analysis for 38 cases. Dermatol Surg 31(4):423–430

    Article  PubMed  CAS  Google Scholar 

  24. Lindstrom AK et al (2008) LRIG1 and squamous epithelial uterine cervical cancer: correlation to prognosis, other tumor markers, sex steroid hormones, and smoking. Int J Gynecol Cancer 18(2):312–317

    Article  PubMed  CAS  Google Scholar 

  25. Thomasson M et al (2011) LRIG1 and the liar paradox in prostate cancer: a study of the expression and clinical significance of LRIG1 in prostate cancer. Int J Cancer 128(12):2843–2852

    Article  PubMed  CAS  Google Scholar 

  26. Guo D et al (2006) Perinuclear leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) as prognostic indicators in astrocytic tumors. Acta Neuropathol 111(3):238–246

    Article  PubMed  CAS  Google Scholar 

  27. Holmlund C et al (2009) Cytoplasmic LRIG2 expression is associated with poor oligodendroglioma patient survival. Neuropathology 29(3):242–247

    Article  PubMed  Google Scholar 

  28. Korhonen K et al (2006) Female predominance in meningiomas can not be explained by differences in progesterone, estrogen, or androgen receptor expression. J Neurooncol 80(1):1–7

    Article  PubMed  CAS  Google Scholar 

  29. Louis DN, Weistler OD, Cavenee WK (2007) WHO classification of tumours of the central nervous system. WHO, Lyon

    Google Scholar 

  30. Kononen J et al (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4(7):844–847

    Article  PubMed  CAS  Google Scholar 

  31. Nilsson J et al (2003) LRIG1 protein in human cells and tissues. Cell Tissue Res 312(1):65–71

    PubMed  CAS  Google Scholar 

  32. Michaud DS et al (2010) Reproductive factors and exogenous hormone use in relation to risk of glioma and meningioma in a large European cohort study. Cancer Epidemiol Biomarkers Prev 19(10):2562–2569

    Article  PubMed  CAS  Google Scholar 

  33. Korhonen K et al (2010) Exogenous sex hormone use and risk of meningioma: a population-based case–control study in Finland. Cancer Causes Control 21(12):2149–2156

    Article  PubMed  CAS  Google Scholar 

  34. Leaes CG et al (2010) Immunohistochemical expression of aromatase and estrogen, androgen and progesterone receptors in normal and neoplastic human meningeal cells. Neuropathology 30(1):44–49

    Article  PubMed  Google Scholar 

  35. Guevara P et al (2010) Angiogenesis and expression of estrogen and progesterone receptors as predictive factors for recurrence of meningioma. J Neurooncol 98(3):379–384

    Article  PubMed  CAS  Google Scholar 

  36. Pravdenkova S et al (2006) Progesterone and estrogen receptors: opposing prognostic indicators in meningiomas. J Neurosurg 105(2):163–173

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Soma Ghasimi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ghasimi, S., Haapasalo, H., Eray, M. et al. Immunohistochemical analysis of LRIG proteins in meningiomas: correlation between estrogen receptor status and LRIG expression. J Neurooncol 108, 435–441 (2012). https://doi.org/10.1007/s11060-012-0856-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-012-0856-x

Keywords

Navigation