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.

Immunohistochemical analysis of p16INK4a, p14ARF, p18INK4c, p21CIP1, p27KIP1 and p73 expression in 271 meningiomas correlation with tumor grade and clinical outcome

“…2 The NF2 gene functions as tumor suppressor gene (negative growth regulator) and merlin, NF2 gene product, is involved in regulating cell proliferation. The data obtained by Perry et al, 15 however, suggest that loss of merlin immuno expression is relatively equally distributed among various meningioma subsets and was not associated specifically with recurrence, proliferation, brain invasion and histological anaplasia. Mutations of other suppressor gene TP53 are extremely rare in meningiomas.…”

Clear cell ependymoma: A clinicopathologic and radiographic analysis of 10 patients

“…DAL-1 originally was implicated in the tumorigenesis of nonsmall cell lung carcinoma and subsequently has been associated with additional malignancies, including glial tumors, meningiomas, and breast carcinoma. 21,[32][33][34] Recently, Singh et al 20 used both FISH and immunohistochemistry to evaluate 27 ependymomas for NF2/merlin and DAL-1/DAL-1 at the DNA and protein levels, respectively. They found NF2/merlin losses limited to spinal ependymomas, whereas the majority of DAL-1/DAL-1 losses were detected in intracranial lesions.…”

Nf2 gene inactivation in arachnoidal cells is rate-limiting for meningioma development in the mouse

“…To preserve the arachnoidal layer, the head was fixed in formalin in toto, decalcified, and sliced coronally before embedding in paraffin. Histological analysis, detection of ␤-galactosidase activity, and immunohistochemistry with affinity purified rabbit polyclonal antibodies against merlin (1:500; WA30; Gutmann et al 1997), DAL-1 (1:500; 3A1; Perry et al 2000), and rat monoclonal anti-GFAP (1:100; Zymed) were performed as described in Giovannini et al (2000).…”