Expression of merlin, NDRG2, ERBB2, and c-MYC in meningiomas: relationship with tumor grade and recurrence

Abstract

Meningiomas are common, usually benign tumors of the central nervous system that have a high rate of post-surgical recurrence or regrowth. We determined expression of the proteins merlin, NDRG2, ERBB2, and c-MYC in meningiomas using immunohistochemistry and assessed relationships between protein expression and gender, age, tumor grade, and recurrence or regrowth. The study sample comprised 60 patients, (44 women and 16 men) with a mean age of 53.2±12.7 years. Tumors were classified as grade I (n=48) or grades II and III (n=12). Expression of merlin, NDRG2, ERBB2, and c-MYC was not significantly different statistically with relation to gender, age, or meningioma recurrence or regrowth. Merlin was expressed in 100% of the cases. No statistically significant difference between tumor grade and recurrence or regrowth was identified. Statistically significant differences were identified between the mean age of patients with grade I (54.83±11.60) and grades II and III (46.58±15.08) meningiomas (P=0.043), between strong c-MYC expression and grades II and III (P<0.001), and between partial surgical resection and tumor recurrence or regrowth (P<0.001). These findings reveal the lower mean age among grades II and III meningioma patients than grade I patients, the influence of the protein merlin on tumorigenesis, the association of c-MYC with aggressive meningiomas, and that partial surgical resection is associated with tumor recurrence or regrowth.

Nervous NDRGs: the N-myc downstream–regulated gene family in the central and peripheral nervous system

“…Although these studies found a strong relationship between loss of NDRG2 expression and tumor grade/recurrence, a larger study by Ongaratti et al (n = 60) did not observe this effect using immunohistochemistry [67]. The lack of reproducibility could have been caused by the small number of meningiomas with invasive and aggressive characteristics in this study (n = 12 for tumor grades II and III combined), or by the fact that the two studies used different antibodies for immunohistochemistry.…”

Investigating the levels of soluble extracellular domain of her2 protein in the sera of meningioma patients

“…Wang et al observed that when the gene expression of HER2 was down-regulated, the proliferative and invasive ability of the meningioma cells were decreased, and these cells had higher rates of apoptosis (24). Moreover, consistent with our results, some studies reported the higher expression of HER2 on the surface of higher grade meningiomas, although they stated no statistical significance for this association (14,15). On the other hand, there are studies that report no correlation between HER2 expression and histological grade and prognosis of meningiomas (17,25), and a few studies have even shown decreased HER2 expression in higher grade meningiomas (3).…”

“…In addition, Wang et al demonstrated that overexpression of HER2 resulted in meningiomas with increased cell invasion, migration, and proliferation, whereas downregulation of HER2 protein expression inhibited the neoplastic cells' motility and proliferation, which led to an increase in apoptosis and arrest cell cycle at the G0/G1-phase (24). In addition, higher expression of HER2 in higher grades of meningioma (grade II, III) in comparison to low-grade tumors (grade I) has been reported (13,15). On the other hand, there are studies that report no association between HER2 expression and meningioma features (14).…”

RNA-seq transcriptome analysis of formalin fixed, paraffin-embedded canine meningioma

“…Among the 42 overexpressed genes in our study, the majority (23 of 42) are associated with dysregulation of gene expression in one or more human cancers. These include, but are not limited to, FOSB [ 40 ], FOS [ 41 ], BMPR1B [ 42 ], WNT5A [ 43 , 44 ], PDPN [ 45 ], BMPER [ 46 ], IRF6 [ 47 ], and MYC [ 48 , 49 ]. Additionally, FOS, MYC, and PDPN have been shown to be overexpressed specifically in meningeal tumors [ 41 , 48 , 50 ].…”