Article
Integrin alpha v beta 3 (αvβ3) expression and MGMT promoter methylation in patients with glioblastoma
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Authors
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Oliver Schnell
- Neurochirurgische Klinik und Poliklinik, Klinikum der Universität München, Campus Großhadern, München
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David Pfirrmann
- Neurochirurgische Klinik und Poliklinik, Klinikum der Universität München, Campus Großhadern, München
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Valerie Albrecht
- Neurochirurgische Klinik und Poliklinik, Klinikum der Universität München, Campus Großhadern, München
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Sabina Eigenbrod
- Institut für Neuropathologie und Prionforschung, Ludwig-Maximilians-Universität München
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Jörg-Christian Tonn
- Neurochirurgische Klinik und Poliklinik, Klinikum der Universität München, Campus Großhadern, München
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Christian Schichor
- Neurochirurgische Klinik und Poliklinik, Klinikum der Universität München, Campus Großhadern, München
| Published: | May 21, 2013 |
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Outline
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Objective: Integrin alpha v beta 3 (αvβ3) is important for invasive tumor growth and angiogenesis in glioblastomas (GBM). In GBM patients with hypermethylation of the MGMT promoter, clinical studies have demonstrated a better prognosis when integrin-inhibitors were added to concommittant radiochemotherapy and adjuvant temozolomide chemotherapy compared to patients with an unmethylated MGMT promoter. Here we study whether a hypermethylated MGMT promoter status correlates with an elevated integrin αvβ3 expression in GBM.
Method: Tumor samples from 39 patients with newly diagnosed, untreated GBM (n=22 with and n=17 without MGMT promoter methylation) were analyzed by immunohistochemistry for integrin αvβ3. In all patients, integrin immunohistochemistry was performed simultaneously by an automated staining platform after histopathological confirmation of a GBM according to the WHO criteria. In order to reach a maximum of accuracy for subsequent semiquantitative analysis a special imaging software, which was calibrated for this purpose, was used. Additionally, ELISA was performed for integrin subunits to confirm the immunohistochemical staining experiments. MGMT promoter methylation status was determined by standard methylation specific PCR (MSP).
Results: Expression of integrin αvβ3 was found to be abundant in endothelial cells but also to a large extent in glial tumor cells in GBM. The semiquantitative analysis of the immunohistochemical staining showed no difference in integrin expression between patients with methylated or unmethylated MGMT promoter status. To further analyze the integrin subunits, ELISA from histologic sections was performed. Again, no difference was detectable in integrin αvβ3 expression between patients with methylated or unmethylated MGMT promoter status.
Conclusions: Tumor tissue of patients with methylated MGMT promoter status does not exhibit higher expression of αvβ3 integrin compared to non-methylated tumors. Thus it has yet to be defined which factors account for the MGMT promoter methylation status related difference in outcome of patients receiving an anti-integrin αvβ3 treatment.
