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Erschienen in: European Spine Journal 11/2014

01.11.2014 | Original Article

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

verfasst von: Reza Akhavan-Sigari, Michael Robert Gaab, Veit Rohde, Mehdi Abili, Helmut Ostertag

Erschienen in: European Spine Journal | Ausgabe 11/2014

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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 %.
Literatur
1.
Zurück zum Zitat Al-Mefty O, Borba LA (1997) Skull base chordomas: a management challenge. J Neurosurg 86(2):182–189PubMedCrossRef Al-Mefty O, Borba LA (1997) Skull base chordomas: a management challenge. J Neurosurg 86(2):182–189PubMedCrossRef
2.
Zurück zum Zitat Mendenhall WM, Mendenhall CM, Lewis SB, Villaret DB, Mendenhall NP (2005) Skull base chordoma. Head Neck 27(2):159–165PubMedCrossRef Mendenhall WM, Mendenhall CM, Lewis SB, Villaret DB, Mendenhall NP (2005) Skull base chordoma. Head Neck 27(2):159–165PubMedCrossRef
3.
Zurück zum Zitat 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)PubMedCrossRef 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)PubMedCrossRef
4.
Zurück zum Zitat Chugh R, Tawbi H, Lucas DR, Biermann JS, Schuetze SM, Baker LH (2007) Chordoma: the nonsarcoma primary bone tumor. Oncologist 12(11):1344–1350PubMedCrossRef Chugh R, Tawbi H, Lucas DR, Biermann JS, Schuetze SM, Baker LH (2007) Chordoma: the nonsarcoma primary bone tumor. Oncologist 12(11):1344–1350PubMedCrossRef
5.
Zurück zum Zitat 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):2086–2097PubMedCrossRef 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):2086–2097PubMedCrossRef
6.
Zurück zum Zitat Hof H, Welzel T, Debus J (2006) Effectiveness of cetuximab/gefitinib in the therapy of a sacral chordoma. Onkologie 29(12):572–574PubMedCrossRef Hof H, Welzel T, Debus J (2006) Effectiveness of cetuximab/gefitinib in the therapy of a sacral chordoma. Onkologie 29(12):572–574PubMedCrossRef
7.
Zurück zum Zitat 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):158–159CrossRef 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):158–159CrossRef
8.
Zurück zum Zitat 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):629–639PubMedCrossRefPubMedCentral 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):629–639PubMedCrossRefPubMedCentral
9.
Zurück zum Zitat 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 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
10.
Zurück zum Zitat 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):577–580CrossRef 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):577–580CrossRef
11.
Zurück zum Zitat 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):175–184CrossRef 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):175–184CrossRef
12.
Zurück zum Zitat 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):118–145CrossRef 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):118–145CrossRef
13.
Zurück zum Zitat 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):2261–2267PubMedCrossRef 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):2261–2267PubMedCrossRef
14.
Zurück zum Zitat Volpe R, Mazabraud A (1983) A clinicopathologic review of 25 cases of chordoma (a pleomorphic and metastasizing neoplasm). Am J Surg Pathol 7(2):161–170PubMedCrossRef Volpe R, Mazabraud A (1983) A clinicopathologic review of 25 cases of chordoma (a pleomorphic and metastasizing neoplasm). Am J Surg Pathol 7(2):161–170PubMedCrossRef
15.
Zurück zum Zitat 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):2122–2134PubMedCrossRef 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):2122–2134PubMedCrossRef
16.
Zurück zum Zitat 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):288–294PubMedCrossRef 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):288–294PubMedCrossRef
17.
Zurück zum Zitat 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):926–930PubMedCrossRef 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):926–930PubMedCrossRef
18.
Zurück zum Zitat 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):1934–1941PubMedCrossRef 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):1934–1941PubMedCrossRef
19.
Zurück zum Zitat 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):1–11PubMedCrossRef 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):1–11PubMedCrossRef
20.
21.
Zurück zum Zitat 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)PubMedCrossRef 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)PubMedCrossRef
22.
Zurück zum Zitat 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 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
23.
Zurück zum Zitat Nicotera P, Bonfoco E, Brüne B (1995) Mechanisms for nitric oxide-induced cell death: involvement of apoptosis. Adv Neuroimmunol 5(4):411–420PubMedCrossRef Nicotera P, Bonfoco E, Brüne B (1995) Mechanisms for nitric oxide-induced cell death: involvement of apoptosis. Adv Neuroimmunol 5(4):411–420PubMedCrossRef
24.
Zurück zum Zitat 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):587–596PubMedCrossRef 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):587–596PubMedCrossRef
25.
Zurück zum Zitat 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):79–88PubMedCrossRef 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):79–88PubMedCrossRef
26.
Zurück zum Zitat 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):835–846PubMedCrossRef 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):835–846PubMedCrossRef
27.
Zurück zum Zitat 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):5395–5402PubMedCrossRef 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):5395–5402PubMedCrossRef
28.
Zurück zum Zitat 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):134–153PubMedCrossRefPubMedCentral 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):134–153PubMedCrossRefPubMedCentral
29.
Zurück zum Zitat 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):2625–2634PubMedCrossRefPubMedCentral 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):2625–2634PubMedCrossRefPubMedCentral
30.
Zurück zum Zitat 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):617–626PubMedCrossRef 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):617–626PubMedCrossRef
31.
Zurück zum Zitat Hanna SA, Aston WJS, Briggs TWR, Cannon SR, Saifuddin A (2008) Sacral chordoma: can local recurrence after sacrectomy be predicted? Clin Orthop 466(9):2217–2223PubMedCrossRefPubMedCentral Hanna SA, Aston WJS, Briggs TWR, Cannon SR, Saifuddin A (2008) Sacral chordoma: can local recurrence after sacrectomy be predicted? Clin Orthop 466(9):2217–2223PubMedCrossRefPubMedCentral
32.
Zurück zum Zitat 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):197–203PubMed 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):197–203PubMed
33.
Zurück zum Zitat Rich TA, Schiller A, Suit HD, Mankin HJ (1985) Clinical and pathologic review of 48 cases of chordoma. Cancer 56(1):182–187PubMedCrossRef Rich TA, Schiller A, Suit HD, Mankin HJ (1985) Clinical and pathologic review of 48 cases of chordoma. Cancer 56(1):182–187PubMedCrossRef
Metadaten
Titel
Prognostic significance of immunohistochemical expression of VEGFR2 and iNOS in spinal chordoma
verfasst von
Reza Akhavan-Sigari
Michael Robert Gaab
Veit Rohde
Mehdi Abili
Helmut Ostertag
Publikationsdatum
01.11.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
European Spine Journal / Ausgabe 11/2014
Print ISSN: 0940-6719
Elektronische ISSN: 1432-0932
DOI
https://doi.org/10.1007/s00586-014-3417-5

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