Prognostic role of Her2/neu, progesterone receptor, and MIB-1 expression in meningioma

Abstract

Background The clinical progress of meningiomas is difficult to predict, and risk stratification on the basis of histomorphology alone remains problematic. Investigators are currently researching numerous predictive and prognostic factors, aiming to facilitate the identification of patients with meningioma who should be followed more closely for evidence of recurrent tumor or may be treated more aggressively at the time of diagnosis.Aim In the current study, we aimed to investigate the relation between Her-2, progesterone receptor (PR), and ki-67 expression in meningiomas and patients' disease-free survival as well as some of the traditional histopathological factors, namely tumor grade and histological subtype.Methods Thirty-eight patients with sporadic intracranial meningiomas were included in the study. Patients were followed up for the time of first relapse or death from disease. The mean follow-up period was 49 months, with a median of 36 months. Original hematoxylin and eosin slides of the tumors were re-examined for histological type and grade. Sections from the paraffin-embedded tumor tissue were immunohistochemically stained for Her 2/neu, Ki67, and PRs. The dilution of the primary antibody was 1:250 for HER2/neu (Polyclonal Rabbit Anti-Human c-erb-B-2 Oncoprotein), 1:200 for ki-67 (MIB-1), and 1:100 for the progesterone receptor (PgR).Results Classical grade I meningiomas accounted for 82% of the studied cases, whereas the remaining 18% were atypical/anaplastic (grade II/III) meningiomas. HER-2 positivity was detected as membranous staining in 13 (34.2%) of the patients. HER-2 positivity for the atypical/ anaplastic meningioma group was (57.1%) as opposed to (29%) for the classical meningioma group. PRs were detected in 18 (47.4%) of the patients, with the classical group showing a (54.8%) positivity as opposed to (14.3%) in the atypical/anaplastic group. Overall, the MIB-1 proliferation index ranged from 0.5 to 18.6, the range was 0.5-2.2 with a mean of 1.197 for grade I meningiomas, whereas the range in the atypical/anaplastic group was 4.6-18.6, with a mean of 10.15. The rate of recurrence was 57% in the atypical/anaplastic group as compared with 23% in the classical meningiomas. On multivariate analysis, a statistically significant relation was found between diseasefree survival and the MIB-1 index and HER-2 expression; 73% of the recurrences occurred in HER-2 positive cases. Also, the mean survival time for HER-2-positive cases was shorter than those patients whose tumors were HER-2 negative (37 vs. 55 months). PR and tumor subtype showed no statistically significant relationship with survival. ConclusionThe study concludes that Her-2/neu expression and the MIB-1 proliferation index can be independent prognostic factors for meningioma patients' disease-free survival. We suggest that patients with tumors showing HER2 positivity and high MIB-1 labeling index should be followed more closely for evidence of tumor recurrence.

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

“…Furthermore, 50% of ERBB2-positive cases experienced recurrence. Khamis et al ( 29 ) reported that 34.2% of 38 meningioma cases were ERBB2-positive, with 29% grade I and 57.1% grades II and III. There was no statistically significant association between ERBB2 expression and tumor grade.…”

Human epidermal growth factor receptor 2/neu protein expression in meningiomas: An immunohistochemical study

“…[ 20 ] studied expression of Erb B1, Erb B2, Erb B3, and Erb B4 receptors and ligand genes by real-time polymerase chain reaction in various grades of meningiomas and found strong erbB1-erbB2 overexpression and erbB3-erbB4 underexpression in meningioma and suggested that these findings might be useful for gene therapy. In another study published in 2011[ 21 ] revealed highest HER2 immunopositivity in meningothelial subtype of meningioma. Atypical/anaplastic meningioma types showed highest rate HER2 immunopositivity than benign meningiomas.…”

Recurrence/Regrowth in Grade I Meningioma: How to Predict?

“…Some studies have shown higher HER2 expressions in grade I meningiomas (116,117), while other studies have shown no significant differences between grades (7,42,53,113,115,118). In some studies, the relation between HER2 expression and an increase in Ki67 and recurrence was evidenced, indicating that they may be predictors of aggression (51,119).…”