Prognostic value of HER2 expression in meningiomas: an immunohistochemical and fluorescence in situ hybridization study

Abstract

The aggressiveness of meningiomas is unpredictable. HER2 represents a well-known prognostic factor in various tumors such as breast carcinomas. This work was designed to study HER2 protein expression and HER2 gene amplification in meningiomas and to evaluate their prognostic value. Frozen sections of 35 meningiomas were immunostained for HER2, estrogen receptor, progesterone receptor, E-cadherin, and MIB-1. Meningiomas immunostained for HER2 were further examined for the HER2 gene amplification by dual-color fluorescence in situ hybridization using probes for centromere 17 and 17q11.2-q12. Complete clinical information was obtained in all cases. The study included 15 atypical meningiomas, 3 anaplastic meningiomas, and 17 classic meningiomas. Five atypical/anaplastic meningiomas and 5 classic meningiomas of the whole 35 (28.5%) meningiomas expressed HER2 protein. This was considered as an overexpression in comparison with negative normal meninges. Fluorescence in situ hybridization demonstrated more HER2 gene copy in 4 of these 10 HER2-positive meningiomas. At equivalent histologic grading, meningiomas with HER2 overexpression exhibited similar immunohistochemical parameters of prognostic value than their HER2-negative counterparts; however, the rate of tumor recurrence was significantly higher in meningiomas with HER2 overexpression than in HER2-negative meningiomas. Conversely, HER2 amplification was not associated with recurrence. Some meningiomas exhibit HER2 protein overexpression in part induced by gene amplification. However, only HER2 overexpression could represent an independent prognostic factor in meningiomas.