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

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Abstract

Background:

Meningiomas are common slow-growing primary central nervous system tumors that arise from the meningothelial cells of the arachnoid and spinal cord. Human epidermal growth factor receptor 2 (HER2) or HER2/neu (also known as c-erbB2) is a 185-kD transmembrane glycoprotein with tyrosine kinase activity expressed in meningiomas and various other tumors. It can be used in targeted therapy for HER2/neu positive meningiomas.

Aim:

To correlate the expression of HER2/neu protein in meningiomas with gender, location, histological subtypes, and grade.

Materials and Methods:

It was 3½ years prospective (March 2010–October 2011) and retrospective (May 2008–February 2010) study of histopathologically diagnosed intracranial and intraspinal meningiomas. Clinical details of all the cases were noted from the computerized hospital information system. Immunohistochemistry for HER2/neu protein was performed along with scoring. Statistical analysis was done using Chi-square test to look for any association of HER2/neu with gender, location, grade, and various histological subtypes of meningiomas at 5% level of significance.

Results:

A total of 100 cases of meningiomas were found during the study period. Of which, 80 were Grade I, 18 were Grade II, and 2 were Grade III meningiomas as per the World Health Organization 2007 criteria. The female-male ratio was 1.9:1 and the mean age was 47.8 years. HER2/neu protein was expressed in 75% of Grade I and 72.2% of Grade II and none of Grade III meningiomas. About 72.7% brain invasive meningiomas showed HER2/neu immunopositivity.

Conclusion:

HER2/neu protein was expressed in 73% of meningiomas. Statistically significant difference of HER2/neu expression was not seen between females and males of Grade I and Grade II/III meningiomas, intracranial and spinal tumors, Grade I and Grade II/III cases, and various histological subtypes of meningiomas.

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Most cited references 21

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"Malignancy" in meningiomas: a clinicopathologic study of 116 patients, with grading implications.

A. PERRY, B. Scheithauer, S Stafford … (1999)

Due to the rarity of malignancy in meningiomas, prior studies have been limited to small series. Controversies regarding the definition of malignant meningioma have complicated matters further. Although histologic anaplasia and extracranial metastasis are established criteria, the former is difficult to define and the latter represents a clinical finding. Traditionally, brain invasion has also been accepted, although this has recently been debated. In a prior series, the authors were unable to prove that 23 meningiomas that had invaded the brain were more aggressive than atypical meningiomas. The authors expanded their analysis to include 116 patients diagnosed with "malignant meningioma" due to brain invasion, frank anaplasia (20 mitoses per 10 high-power fields or histology resembling carcinoma, sarcoma, or melanoma), and/or extracranial metastasis. Patients were followed until death or for a median of 3.7 years. Survival time was highly variable, ranging from 10 days to 24 years. In multivariate analysis, histologic anaplasia (P=0.0035), subtotal resection (P=0.0038), 20 mitoses per 10 high-power fields (P=0.0071), and nuclear atypia (P=0.0068) were associated with poor survival. Of the 89 cases of meningioma that had invaded the brain, 23% were otherwise benign, 61% were otherwise atypical, and 17% were frankly anaplastic. Those without anaplasia behaved similarly to atypical meningiomas from the authors' prior study. In contrast, anaplastic meningiomas were usually fatal, associated with a median survival of 1.5 years. Based on these findings, the authors suggest that brain invasion constitutes an additional criterion for the diagnosis of atypical meningioma (World Health Organization [WHO] Grade II), whereas frank anaplasia indicates high grade (WHO Grade III-IV) malignancy.

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Epidermal growth factor receptor family (EGFR, ErbB2-4) in gliomas and meningiomas.

Thomas Brännström, Roger Henriksson, Dongsheng Guo … (2004)

Overexpression of epidermal growth factor receptor (EGFR, ErbB1) correlates with enhanced malignant potential of many human tumor types including glioblastoma multiforme. The significance of EGFR expression in meningiomas is, however, unclear. Reports regarding the other EGFR family members, ErbB2-4, in brain tumors are sparse. In this study, the expression of the EGFR family members was analyzed in relation to various parameters for the clinical importance of these receptors in 44 gliomas and 26 meningiomas. In gliomas, quantitative real-time reverse transcription (RT)-PCR revealed the highest EGFR mRNA expression in high-grade gliomas, while ErbB2 and ErbB3 mRNA were detected only in a few high-grade gliomas. In contrast, ErbB4 expression was most pronounced in low-grade gliomas. Immunohistochemistry showed significantly higher EGFR protein expression in high-grade gliomas compared to low-grade gliomas (P= 0.004). ErbB2 protein expression was mainly seen in high-grade gliomas. ErbB3 protein expression was low in all gliomas analyzed. ErbB4 protein expression was significantly higher in low-grade gliomas than in high-grade gliomas (P= 0.007). In meningiomas, quantitative real-time RT-PCR revealed expression of EGFR, ErbB2, and ErbB4 mRNA in the majority of the tumors. ErbB3 was detected in only one of the meningiomas analyzed. Immunohistochemistry demonstrated high ErbB2 protein expression in meningiomas. An intriguing observation in astrocytomas and oligodendrogliomas grade II, was a significantly decreased overall survival for patients with high EGFR protein expression (P= 0.04). The high ErbB4 expression in low-grade compared to high-grade gliomas might suggest that ErbB4 acts as a suppressor of malignant transformation in brain tumors, which is in line with previous studies in other tumor types.

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The benefit of HER2-targeted therapies on overall survival of patients with metastatic HER2-positive breast cancer – a systematic review

Diogo Mendes, Carlos Alves, Noémia Afonso … (2015)

Introduction This study aimed at evaluating the overall survival (OS) gain associated with human epidermal growth factor receptor 2 (HER2)-directed therapies in patients with metastatic breast cancer (mBC). Methods A bibliographic search was conducted in PubMed and Cochrane databases. Only phase III randomized controlled trials (RCTs) including HER2-positive (HER2+) mBC patients were included in this review. OS was defined as time from randomization until the occurrence of death from any cause. Studies have been grouped according to the line of treatment, i.e., first-line or second-line or beyond. Results Nineteen RCTs were eligible for inclusion, of which 12 assessed therapies targeting HER2+ mBC in the first-line setting. OS improved from 20.3 months in the first RCT (standard chemotherapy; Slamon et al. (N Engl J Med 344:783–92, 2001)) evaluating HER2-targeting therapies to 48 months in the study of Swain et al. (Lancet Oncol 14:461–71, 2013), with triple combination of pertuzumab, trastuzumab and docetaxel. Seven RCTs evaluated the OS of HER2-targeting therapies in the second-line setting and beyond. The OS in second-line setting improved from 15.3 months (capecitabine; Cameron et al. (Breast Cancer Res Treat 112:533–43, 2008)) to 30.7 months (trastuzumab emtansine; Verma et al. (N Engl J Med 367:1783–91, 2012)). In the third-line setting, the association of lapatinib and trastuzumab has demonstrated to improve OS to 4.5 months compared with lapatinib alone (14 months vs. 9.5 months; Blackwell et al. (J Clin Oncol 30:2585–92, 2012)). Conclusions HER2-directed therapies had an undeniable beneficial impact on the OS of patients with HER2+ mBC. The triple combination of docetaxel, pertuzumab and trastuzumab is associated with a survival extent of more than 4.5 years, compared with a life expectancy of 1.5 years achieved 14 years ago. Electronic supplementary material The online version of this article (doi:10.1186/s13058-015-0648-2) contains supplementary material, which is available to authorized users.

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Author and article information

Journal

Journal ID (nlm-ta): J Neurosci Rural Pract

Journal ID (iso-abbrev): J Neurosci Rural Pract

Journal ID (publisher-id): JNRP

Title: Journal of Neurosciences in Rural Practice

Publisher: Medknow Publications & Media Pvt Ltd (India )

ISSN (Print): 0976-3147

ISSN (Electronic): 0976-3155

Publication date (Print): Oct-Dec 2016

Volume: 7

Issue: 4

Pages: 526-531

Affiliations

[1] Department of Pathology, Christian Medical College Hospital, Vellore, Tamil Nadu, India

[1 ] Department of Pathology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India

[2 ] Department of Neurosurgery, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India

Author notes

Address for correspondence: Dr. Amit Kumar Chowhan, Department of Pathology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India. E-mail: chowhanpath@ 123456gmail.com

Article

Publisher ID: JNRP-7-526

DOI: 10.4103/0976-3147.188640

PMC ID: 5006463

PubMed ID: 27695231

SO-VID: bf2282f0-1438-44b6-bae1-855ad13e721d

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This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

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

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Most cited references 21

"Malignancy" in meningiomas: a clinicopathologic study of 116 patients, with grading implications.

Epidermal growth factor receptor family (EGFR, ErbB2-4) in gliomas and meningiomas.

The benefit of HER2-targeted therapies on overall survival of patients with metastatic HER2-positive breast cancer – a systematic review

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