17IN - Classification and molecular pathology of meningiomas

Date 28 September 2014
Event ESMO 2014
Session Current concepts and future avenues in meningioma
Topics Central Nervous System Malignancies
Pathology/Molecular Biology
Presenter Christian Mawrin
Citation Annals of Oncology (2014) 25 (suppl_4): iv8-iv8. 10.1093/annonc/mdu293
Authors C. Mawrin
  • Neuropathology, Otto-von Guericke-Universität, 39120 - Magdeburg/DE

Abstract

Body

Abstract:

Meningiomas are the most frequent intracranial tumors. About 80 percent of meningiomas belong to the group of WHO [World Health Organization] grade I tumors, but a significant number of tumors is graded as atypical WHO grade II (∼20 percent) or anaplastic grade III (∼1%) meningiomas, respectively. Even the WHO grade I group covers 9 different histological subtypes, and grade II/III meningiomas comprise 7 different subtypes. Grade II/III meningiomas are associated with significantly increased morbidity and mortality. A major risk factor for the frequently occurring meningioma recurrences is brain invasion.

Based on the observation that patients suffering from neurofibromatosis type 2 (NF2) frequently develop meningiomas, loss of the NF2 gene located on chromosome 22q with its gene product merlin was identified as the most important genetic event associated with meningioma development. NF2 alterations can be found in about 40-50 percent of sporadic meningiomas, and mouse models have proven that NF2 loss is the initial step necessary for meningioma tumorigenesis. Other recently identified genetic alterations in sporadic grade I meningiomas affects genes like Smo, AKT, TRAF7, and KLF4. Their contribution to meningioma development and -growth is unclear thus far, but they are exclusively found in NF2 wild-type tumors.

The progression to aggressive meningioma subtypes (grade II/III) is linked to inactivation of tumor suppressor genes at 1p, 9p, 10q and 14q. Alterations of the genes CDKN2A / CDKN2B genes on chromosome 9p have been demonstrated to be exceptionally relevant. Other progression-associated changes are loss of progesterone receptor expression, inactivation of TIMP3, loss of DAL1/protein 4.1B, reduced expression of NDRG2 and MEG3, and increased telomerase activity.

Disclosure:

The author has declared no conflicts of interest.