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Expression of cyclooxygenase-2 and epidermal growth factor receptor in primary and recurrent glioblastoma multiforme

Abstract

Purpose: To investigate the pattern and level of cyclooxygenase-2 (COX-2) expression in a series of high grade primary and recurrent glioblastoma multiforme (GBM) and correlation with time to recurrence and patients’ survival following therapy. The relationship between COX-2 and epidermal growth factor receptor (EGFR) immunoreactivities was evaluated. Materials and methods: Specimens of 14 primary and 14 recurrent GBMs (eight pairs) following surgery and full course radiation therapy were processed for immunostaining on COX-2 and EGFR. Tumor cell positivity was semi-quantitatively scored. COX-2 scores of the primary tumor and recurrence were correlated with the time to radiological tumor progression and patients’ survival. Results: COX-2 positive tumor cells were disseminated throughout the tumor parenchyma. The intensity and pattern of COX-2 expression were heterogeneous, with predominant expression in areas surrounding tumor necrosis. Scoring of COX-2 positivity revealed values between 1 and 80% of the cells. Primary GBMs with COX-2 expression levels between 25% and 70% of the tumor cells showed a shorter time to radiological recurrence than GBMs with <10% COX-2 positive tumor cells (respectively, 219±50 and 382±77 days). No correlation was found between the COX-2 expression in the primary tumor and patients’ survival (r s=−0.073) following therapy. No correlation was found either between COX-2 and EGFR immunoreactivity. Conclusions: Immunohistochemical expression of COX-2 in GBM showed large variation. Hence, determination of COX-2 expression in tumor specimen for each individual might be relevant for selection of those patients, who could benefit from adjuvant therapy with selective COX-2 inhibitors.

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Acknowledgements

Prof. Dr. D. Troost and Ing. M. Ramkema (Department of Neuropathology, Academic Medical Center, Amsterdam, The Netherlands) are kindly acknowledged for providing tumor sections from two patients, and Dr. L.J.A. Stalpers (Department of Radiation Oncology, Academic Medical Center, Amsterdam, The Netherlands) for the follow-up data. Thanks are due to Dr. J.J. Hoozemans for expert advice on the immunostainings and to the division of Photography (Department of Pathology of the VU University medical center) for the microscopical photos.

T.R. Stoter was supported by the Vanderes Foundation (project #49).

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Correspondence to Peter Sminia.

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Sminia, P., Stoter, T.R., van der Valk, P. et al. Expression of cyclooxygenase-2 and epidermal growth factor receptor in primary and recurrent glioblastoma multiforme. J Cancer Res Clin Oncol 131, 653–661 (2005). https://doi.org/10.1007/s00432-005-0020-5

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Keywords

  • COX-2
  • EGFR
  • Primary and recurrent glioblastoma multiforme
  • Immunohistochemistry