Association between absence of epidermal growth factor receptor immunoreactivity and poor prognosis in patients with atypical meningioma

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Object

The clinical behavior of meningiomas is variable. Because multiple growth factor receptors have been identified in these tumors, the authors sought to assess the capacity of the expression patterns of a subset of these receptors to stratify meningioma cases.

Methods

Eighty-four meningiomas were analyzed, including 36 benign, 29 atypical, and 19 malignant lesions. Immunohistochemical staining was performed for epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR)–β, basic fibroblast growth factor receptor (BFGFR), and MIB-1. Survival analyses were performed using follow-up data obtained in patients with newly diagnosed tumors.

Immunoreactivity for EGFR was observed in 47% of benign, 48% of atypical, and 42% of malignant tumors. Staining for BFGFR was identified in 89% of benign, 97% of atypical, and 95% of malignant lesions. Immunostaining for PDGFR-β was evident in all the lesions assessed. Mean MIB-1 indices for benign, atypical, and malignant cases were 3.6 (range 0.5–15.3), 8.2 (range 1.5–23.1) and 18.3 (range 1.0–55.8), respectively. Overall mean follow-up duration was 9.0 years (range 5.1–18.8 years). Lack of EGFR immunoreactivity was identified as a strong predictor of shorter overall survival in patients with atypical meningioma (p = 0.003, log-rank test). This association was not evident in cases of benign or malignant meningiomas.

Conclusions

There is a significant association between EGFR immunoreactivity and prolonged survival in patients with atypical meningioma. Given the variable behavior of atypical meningiomas, EGFR assessment could improve existing strategies for patient stratification and treatment.

Abbreviations used in this paper:BFGF = basic fibroblast growth factor; BFGFR = BFGF receptor; EGF = epidermal growth factor; EGFR = EGF receptor; PDGF = platelet-derived growth factor; PDGFR = PDGF receptor; WHO = World Health Organization.

Article Information

Address reprint requests to: Justin S. Smith, M.D., Ph.D., Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Avenue, M-779, San Francisco, California 94143-0112. email: jsmith1enator@gmail.com.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Photomicrographs showing representative examples of immunohistochemical staining in tumor specimens. A: Example of EGFR immunostaining in a benign (Grade I) meningioma. Staining is diffuse and spares the stromal elements. B: Example of EGFR immunostaining in a benign (Grade I) meningioma, highlighting the presence of both membrane-associated staining (center of image) and cytoplasmic staining. C: Example of PDGFR-β immunostaining. Note the intense staining pattern in this malignant (Grade III) meningioma. D: Example of BFGFR immunostaining in a malignant (Grade III) meningioma. Original magnifications × 100 (A), × 200 (B), and × 250 (C and D).

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    Graphs showing results of EGFR, PDGFR-β, and BFGFR immunohistochemical analysis in 84 meningiomas. A: Overall summary of incidence of immunopositivity by tumor grade for 36 benign, 29 atypical, and 19 malignant meningiomas. B: Percentage of EGFR-positive cells by histological grade (17 benign, 14 atypical, and eight malignant tumors). (Tumors that did not demonstrate positive staining for EGFR were not included.) C: Intensity of PDGFR-β immunostaining by tumor grade. Although all tumors assessed demonstrated PDGFR-β immunostaining, the intensity ranged from weak (Grade 1) to strong (Grade 3). D: Intensity of BFGFR immunostaining by tumor grade. The vast majority of tumors assayed demonstrated BFGFR immunostaining, with the majority of these showing either moderate (Grade 2) or strong (Grade 3) staining intensity.

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    Graph illustrating the duration of survival of patients with atypical meningioma stratified by presence (12 patients) or absence (nine patients) of EGFR immunohistochemical staining. At the last assessment of status, all of the patients whose tumors demonstrated EGFR immunopositivity were alive, while two thirds (six of nine) of the patients whose tumors lacked EGFR immunoreactivity had died (p = 0.003, log-rank test).

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