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

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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 disease-free 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.

Conclusion

The 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.

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