Expression of ezrin, MMP-9, and COX-2 in 50 chordoma specimens: a clinical and immunohistochemical analysis.
METHODS
Retrospective study.


OBJECTIVE
To investigate the immunohistochemical expression profile of ezrin, matrix metalloproteinase-9 (MMP-9), and cyclooxygenase-2 (COX)-2 in chordomas.


BACKGROUND
Ezrin, 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.


METHODS
Fifty 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.


RESULTS
Ezrin 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).


CONCLUSIONS
En 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.
Department of Orthopaedic Surgery, Medical University of Graz, Graz, Austria
Elke Verena
EV
Froehlich
Susanne
S
Scheipl
Aron
A
Lazàry
Peter Pal
PP
Varga
Christoph
C
Schmid
Heinz
H
Stammberger
Alfred
A
Beham
Koppany
K
Bodo
Heribert
H
Schroettner
Franz
F
Quehenberger
Reinhard
R
Windhager
Bernadette
B
Liegl
Andreas
A
Leithner
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001317:Austria; D014408:Biomarkers, Tumor / Q000032:analysis*; D002817:Chordoma / Q000201:enzymology* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D051546:Cyclooxygenase 2 / Q000032:analysis*; D003598:Cytoskeletal Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D006814:Hungary; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012888:Skull Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D013125:Spinal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D013997:Time Factors; D047368:Tumor Burden; D055815:Young Adult; D000099149:Ezrin
D014408:Biomarkers, Tumor; D051546:Cyclooxygenase 2; D003598:Cytoskeletal Proteins; D020780:Matrix Metalloproteinase 9; D000099149:Ezrin; C496540:PTGS2 protein, human