Prognostic value of ErbB2/HER2 in human meningiomas

Abstract

Introduction: Among clinical challenges regarding human meningiomas is their propensity to recur even in cases with benign histology. Reliable biomarkers that can identify these cases are therefore highly desired. ErbB2/HER2 status is important in the medical management of patients with various human malignancies, whereas its clinical relevance in human meningiomas is ambiguous. For this reason, we wanted to investigate the expression of intra- and extracellular domains of ErbB2/HER2 as well as the level of activated receptor in these tumors. Further, we wanted to elucidate any clinicopathological associations to antibody expression and if gene amplification was present.

Methods: In total, 186 human meningiomas of all malignancy grades were included in the study, 163 of these were in tissue microarrays (TMA). Antibody expression was assessed by means of immunohistochemistry (IHC) and gene amplification by fluorescence in situ hybridization (FISH).

Results: All cases were immunoreactive with antibodies targeting the intracellular domain, whereas about 48% and 11% were positive with antibodies against the extracellular domain and against the activated receptor, respectively. Normal meninges were not immunoreactive. There were no relations to malignancy grade, and only the activated receptor was significantly correlated with increased risk for recurrence or death (time to recurrence: HR 1.568, CI (1.153 to 2.132), p = 0.004). No gene amplification was found.

Conclusion: ErbB2/HER2 is generally upregulated in human meningiomas, but in an activated state only in a few cases. Only the activated receptor is associated with poorer prognosis, a link that needs further investigations.

Fig 1. HER2 immunostainings. The pictures were taken with a Nikon eclipse 80i microscope, Lumenera’s Infinity2 camera, and Infinity Analyze software. Magnification: 400x. Microsoft Paint was used to create the final composite image.

a. CB11, SI 9 b. 3B5, SI 9 c. SP3, SI 6 d. 6B12, SI 3.

Fig 2. FISH, angiomatous meningioma grade I. Ratio: 1.25. The picture was taken by MBA through a Nikon eclipse 90i microscope.

Green signals: centromere 17. Red signals: HER2.