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Prognostic significance of immunohistochemical expression of VEGFR2 and iNOS in spinal chordoma

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Abstract

Purpose

To clarify whether vascular endothelial growth factor receptor 2 (VEGFR2) and inducible nitric oxide synthase (iNOS) are involved in the angiogenesis and recurrence of spinal chordoma tissues and influence the overall survival.

Methods

All patients affected by a spinal chordoma surgically treated between 1986 and 2007 were reviewed. We examined the expression of VEGFR2 and iNOS with immunohistochemistry using a tissue microarray containing 120 chordoma samples. Local recurrence and overall survival (OS) were analyzed.

Results

A series of 40 chordoma patients who underwent surgery for a total of 120 lesions (including 80 recurrent lesions) were identified (sacrum 77.5 %, lumbar spine 17.5 %, cervical/thoracic spine 5 %). Surgical margins were wide in 30 (75 %), marginal in 8 (20 %) and intralesional in 2 (5 %) patients. Median follow-up was 120 months. The 5- and 10-year OS of the entire series of patients was 78.6 and 30 %, respectively. There were five primary chordomas (12.5 %) with moderate and 35 (87.5 %) with strong expression of VEGFR-2. All recurrent spinal chordomas displayed strong expression of VEGFR-2. The expression of iNOS was predominately moderate to high in primary chordomas: There were 15 tumors (37.5 %) with moderate and 25 tumors (62.5 %) with strong expression. All recurrent chordomas displayed strong expression of iNOS.

Conclusion

The high expression of VEGFR-2 and iNOS affected the OS. The OS at 10 years was only 30 %.

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References

  1. Al-Mefty O, Borba LA (1997) Skull base chordomas: a management challenge. J Neurosurg 86(2):182–189

    Article  PubMed  CAS  Google Scholar 

  2. Mendenhall WM, Mendenhall CM, Lewis SB, Villaret DB, Mendenhall NP (2005) Skull base chordoma. Head Neck 27(2):159–165

    Article  PubMed  Google Scholar 

  3. Tzortzidis F, Elahi F, Wright D, Natarajan SK, Sekhar LN (2006) Patient outcome at long-term follow-up after aggressive microsurgical resection of cranial base chordomas. Neurosurgery 59(2):230–237 (discussion 230–237)

    Article  PubMed  Google Scholar 

  4. Chugh R, Tawbi H, Lucas DR, Biermann JS, Schuetze SM, Baker LH (2007) Chordoma: the nonsarcoma primary bone tumor. Oncologist 12(11):1344–1350

    Article  PubMed  Google Scholar 

  5. Casali PG, Messina A, Stacchiotti S, Tamborini E, Crippa F, Gronchi A, Orlandi R, Ripamonti C, Spreafico C, Bertieri R, Bertulli R, Colecchia M, Fumagalli E, Greco A, Grosso F, Olmi P, Pierotti MA, Pilotti S (2004) Imatinib mesylate in chordoma. Cancer 101(9):2086–2097

    Article  PubMed  CAS  Google Scholar 

  6. Hof H, Welzel T, Debus J (2006) Effectiveness of cetuximab/gefitinib in the therapy of a sacral chordoma. Onkologie 29(12):572–574

    Article  PubMed  Google Scholar 

  7. Lindén O, Stenberg L, Kjellén E (2009) Regression of cervical spinal cord compression in a patient with chordoma following treatment with cetuximab and gefitinib. Acta Oncol Stockh Swed 48(1):158–159

    Article  Google Scholar 

  8. Miettinen M, Rikala M-S, Rys J, Lasota J, Wang Z-F (2012) Vascular endothelial growth factor receptor 2 as a marker for malignant vascular tumors and mesothelioma: an immunohistochemical study of 262 vascular endothelial and 1640 nonvascular tumors. Am J Surg Pathol 36(4):629–639

    Article  PubMed  PubMed Central  Google Scholar 

  9. Rimm DL, Camp RL, Charette LA, Costa J, Olsen DA, Reiss M (2001) Tissue microarray: a new technology for amplification of tissue resources. Cancer J Sudbury Mass 7(1):24–31

    CAS  Google Scholar 

  10. Hsu SM, Raine L, Fanger H (1981) Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem Off J Histochem Soc 29(4):577–580

    Article  CAS  Google Scholar 

  11. Vanhoefer U, Tewes M, Rojo F, Dirsch O, Schleucher N, Rosen O, Tillner J, Kovar A, Braun AH, Trarbach T, Seeber S, Harstrick A, Baselga J (2004) Phase I study of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with advanced solid tumors that express the epidermal growth factor receptor. J Clin Oncol Off J Am Soc Clin Oncol 22(1):175–184

    Article  CAS  Google Scholar 

  12. Wolff AC, Hammond MEH, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF, American Society of Clinical Oncology, und College of American Pathologists (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol Off J Am Soc Clin Oncol 25(1):118–145

    Article  CAS  Google Scholar 

  13. O’Connell JX, Renard LG, Liebsch NJ, Efird JT, Munzenrider JE, Rosenberg AE (1994) Base of skull chordoma. A correlative study of histologic and clinical features of 62 cases. Cancer 74(8):2261–2267

    Article  PubMed  Google Scholar 

  14. Volpe R, Mazabraud A (1983) A clinicopathologic review of 25 cases of chordoma (a pleomorphic and metastasizing neoplasm). Am J Surg Pathol 7(2):161–170

    Article  PubMed  CAS  Google Scholar 

  15. Bergh P, Kindblom LG, Gunterberg B, Remotti F, Ryd W, Meis-Kindblom JM (2000) Prognostic factors in chordoma of the sacrum and mobile spine: a study of 39 patients. Cancer 88(9):2122–2134

    Article  PubMed  CAS  Google Scholar 

  16. Naka T, Boltze C, Kuester D, Samii A, Herold C, Ostertag H, Iwamoto Y, Oda Y, Tsuneyoshi M, Roessner A (2005) Intralesional fibrous septum in chordoma: a clinicopathologic and immunohistochemical study of 122 lesions. Am J Clin Pathol 124(2):288–294

    Article  PubMed  Google Scholar 

  17. Naka T, Boltze C, Kuester D, Schulz T-O, Samii A, Herold C, Ostertag H, Roessner A (2004) Expression of matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, cathepsin B, and urokinase plasminogen activator in non-skull base chordoma. Am J Clin Pathol 122(6):926–930

    Article  PubMed  CAS  Google Scholar 

  18. Naka T, Boltze C, Samii A, Herold C, Ostertag H, Iwamoto Y, Oda Y, Tsuneyoshi M, Kuester D, Roessner A (2003) Skull base and nonskull base chordomas: clinicopathologic and immunohistochemical study with special reference to nuclear pleomorphism and proliferative ability. Cancer 98(9):1934–1941

    Article  PubMed  Google Scholar 

  19. McMaster ML, Goldstein AM, Bromley CM, Ishibe N, Parry DM (2001) Chordoma: incidence and survival patterns in the United States, 1973–1995. Cancer Causes Control CCC 12(1):1–11

    Article  PubMed  CAS  Google Scholar 

  20. Salisbury JR (1993) The pathology of the human notochord. J Pathol 171(4):253–255

    Article  PubMed  CAS  Google Scholar 

  21. Barry JJ, Jian BJ, Sughrue ME, Kane AJ, Mills SA, Tihan T, Parsa AT (2011) The next step: innovative molecular targeted therapies for treatment of intracranial chordoma patients. Neurosurgery 68(1):231–240 (discussion 240–241)

    Article  PubMed  Google Scholar 

  22. Song Z-J, Gong P, Wu Y-E (2002) Relationship between the expression of iNOS, VEGF, tumor angiogenesis and gastric cancer. World J Gastroenterol WJG 8(4):591–595

    CAS  Google Scholar 

  23. Nicotera P, Bonfoco E, Brüne B (1995) Mechanisms for nitric oxide-induced cell death: involvement of apoptosis. Adv Neuroimmunol 5(4):411–420

    Article  PubMed  CAS  Google Scholar 

  24. Gallo O, Masini E, Morbidelli L, Franchi A, Fini-Storchi I, Vergari WA, Ziche M (1998) Role of nitric oxide in angiogenesis and tumor progression in head and neck cancer. J Natl Cancer Inst 90(8):587–596

    Article  PubMed  CAS  Google Scholar 

  25. Akhavan-Sigari R, Gaab MR, Rohde V, Brandis A, Tezval H, Abili M, von Eckardstein K, Ostertag H (2013) Expression of vascular endothelial growth factor receptor 2 (VEGFR-2), inducible nitric oxide synthase (iNOS), and Ki-M1P in skull base chordoma: a series of 145 tumors. Neurosurg Rev 37(1):79–88

    Article  PubMed  Google Scholar 

  26. Millauer B, Wizigmann-Voos S, Schnürch H, Martinez R, Møller NP, Risau W, Ullrich A (1993) High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 72(6):835–846

    Article  PubMed  CAS  Google Scholar 

  27. Minami T, Rosenberg RD, Aird WC (2001) Transforming growth factor-beta 1-mediated inhibition of the flk-1/KDR gene is mediated by a 5′-untranslated region palindromic GATA site. J Biol Chem 276(7):5395–5402

    Article  PubMed  CAS  Google Scholar 

  28. Kaur B, Khwaja FW, Severson EA, Matheny SL, Brat DJ, Van Meir EG (2005) Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis. Neuro-Oncol 7(2):134–153

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  29. Ziche M, Morbidelli L, Choudhuri R, Zhang HT, Donnini S, Granger HJ, Bicknell R (1997) Nitric oxide synthase lies downstream from vascular endothelial growth factor-induced but not basic fibroblast growth factor-induced angiogenesis. J Clin Invest 99(11):2625–2634

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  30. Zhang N, Fang Z, Contag PR, Purchio AF, West DB (2004) Tracking angiogenesis induced by skin wounding and contact hypersensitivity using a Vegfr2-luciferase transgenic mouse. Blood 103(2):617–626

    Article  PubMed  CAS  Google Scholar 

  31. Hanna SA, Aston WJS, Briggs TWR, Cannon SR, Saifuddin A (2008) Sacral chordoma: can local recurrence after sacrectomy be predicted? Clin Orthop 466(9):2217–2223

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  32. Wakao N, Imagama S, Ito Z, Ando K, Hirano K, Tauchi R, Muramoto A, Matsui H, Matsumoto T, Matsuyama Y, Ishiguro N (2011) Total en bloc spondylectomy for L2 chordoma: a case report. Nagoya J Med Sci 73(3–4):197–203

    PubMed  Google Scholar 

  33. Rich TA, Schiller A, Suit HD, Mankin HJ (1985) Clinical and pathologic review of 48 cases of chordoma. Cancer 56(1):182–187

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neurosurgery, University Medical Center Göttingen, Georg-August-University Göttingen, Robert-Koch-Strasse 40, 37075, Göttingen, Germany

    Reza Akhavan-Sigari & Veit Rohde

  2. Department of Neurosurgery, Nordstadt Medical Center, Klinikum Hannover, Haltenhoffstr. 41, 30167, Hannover, Germany

    Michael Robert Gaab

  3. Department of Neurosurgery, Mashhad University of Medical Sciences, Taleghani hospital, Shahid Kalantari Avenue, After Ghaem Bridge, Mashhad, Iran

    Mehdi Abili

  4. Department of Pathology, Nordstadt Medical Center, Klinikum Hannover, Haltenhoffstr. 41, 30167, Hannover, Germany

    Helmut Ostertag

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  1. Reza Akhavan-Sigari
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  2. Michael Robert Gaab
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  4. Mehdi Abili
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Correspondence to Reza Akhavan-Sigari.

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Akhavan-Sigari, R., Gaab, M.R., Rohde, V. et al. Prognostic significance of immunohistochemical expression of VEGFR2 and iNOS in spinal chordoma. Eur Spine J 23, 2416–2422 (2014). https://doi.org/10.1007/s00586-014-3417-5

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  • DOI: https://doi.org/10.1007/s00586-014-3417-5

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