title: Merlin, DAL-1, and progesterone receptor expression in clinicopathologic subsets of meningioma: a correlative immunohistochemical study of 175 cases.
abstract: The molecular pathogenesis of meningiomas is poorly characterized. Loss of NF2 (merlin) expression has been reported in 30%-80% of all sporadic meningiomas. Recently, we found that loss of expression for a second Protein 4.1-family tumor suppressor. DAL-1, is also common. A biologically important role for progesterone receptor (PR) has also been proposed based on its reported inverse relationship with tumor grade. In order to better define the pathogenetic roles of these proteins, we studied the merlin, DAL-1, and PR immunoprofiles in 175 fully characterized meningiomas, including nonrecurring versus recurring benign, proliferative versus brain invasive atypical and anaplastic subtypes. Loss of expression for either Protein 4.1-family tumor suppressor (merlin or DAL-1) was almost universal (92%), with combined losses being common (58%). Individually, absence of merlin or DAL-1 protein was detected in 74% and 76% respectively, with no significant differences among the 5 subsets. PR immunoreactivity was commonly associated with retained DAL-1 expression (p < 0.001) and with tumor grade, with 51% of benign, 21% of atypical, and 11% of anaplastic tumors staining positive (p < 0.001). We conclude that PR immunohistochemistry may have diagnostic utility in meningothelial neoplasms. Protein 4.1-family tumor suppressor losses are likely important early events in meningioma pathogenesis, whereas PR expression is associated with benignity.
authors.affiliation: Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110-1093, USA.
authors.forename: A
authors.initials: A
authors.lastname: Perry
authors.forename: D X
authors.initials: DX
authors.lastname: Cai
authors.forename: B W
authors.initials: BW
authors.lastname: Scheithauer
authors.forename: P E
authors.initials: PE
authors.lastname: Swanson
authors.forename: C M
authors.initials: CM
authors.lastname: Lohse
authors.forename: I F
authors.initials: IF
authors.lastname: Newsham
authors.forename: A
authors.initials: A
authors.lastname: Weaver
authors.forename: D H
authors.initials: DH
authors.lastname: Gutmann
mesh_terms: D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000032:analysis* / Q000235:genetics; D008577:Meningeal Neoplasms / Q000737:chemistry* / Q000473:pathology; D008579:Meningioma / Q000737:chemistry* / Q000473:pathology; D008840:Microfilament Proteins; D025581:Neurofibromin 2; D010641:Phenotype; D011980:Receptors, Progesterone / Q000032:analysis* / Q000235:genetics; D025521:Tumor Suppressor Proteins
chemical_list: C116887:EPB41L3 protein, human; D008565:Membrane Proteins; D008840:Microfilament Proteins; D025581:Neurofibromin 2; D011980:Receptors, Progesterone; D025521:Tumor Suppressor Proteins