• Elke Verena Froehlich, Susanne Scheipl, Aron Lazàry, Peter Pal Varga, Christoph Schmid, Heinz Stammberger, Alfred Beham, Koppany Bodo, Heribert Schroettner, Franz Quehenberger, Reinhard Windhager, Bernadette Liegl, and Andreas Leithner.
• Department of Orthopaedic Surgery, Medical University of Graz, Graz, Austria
• Spine. 2012 Jun 1;37(13):E757-67.

Study DesignRetrospective study.ObjectiveTo investigate the immunohistochemical expression profile of ezrin, matrix metalloproteinase-9 (MMP-9), and cyclooxygenase-2 (COX)-2 in chordomas.Summary Of Background DataEzrin, MMP-9, and COX-2 are expressed in different solid tumors, including chordomas. This study investigates the immunohistochemical expression of the aforementioned biomarkers and the clinical outcome in regard to immunohistochemistry, tumor volume, and localization.MethodsFifty brachyury-verified chordoma specimens of 34 primary and 16 recurrent tumors of 44 patients were tested for ezrin, MMP-9, and COX-2 as possible therapeutical targets by immunohistochemistry. The clinical evaluation concentrated on tumor location, volume, and age-related data.ResultsEzrin expression was detected in 33 of 34 primary chordomas and in 16 of 16 recurrent cases. The primary chordomas located in the sacrum and the spine demonstrated a significantly higher percentage of positively stained tumor cells (P = 0.034) than the skull-based chordomas. An expression of MMP-9 and COX-2 was observed in 33 of 34 primary chordomas and in 16 of 16 recurrences, and in 13 of 34 primary chordomas and in 11 of 16 recurrences, respectively. Patients' survival was significantly influenced by age (P = 0.01), tumor location (P = 0.029), and tumor volume (P = 0.002). A significant positive correlation between tumor volume and the anatomic distance of the chordoma from the skull was calculated (P = 0.00002).ConclusionEn bloc resection with tumor-free margins is seldom feasible, particularly in the sacrum. Intralesional excisions mostly end in early local recurrence; therefore, the demand for further treatment options is frequently posed. The marked trend of the investigated biomarkers of this study may build a starting point for further investigations as molecular targets for future adjuvant therapies in chordomas. Future multicenter studies on larger patients' series are necessary to elucidate these preliminary data and to test new treatment options for patients with chordomas.

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