This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Smith, B. D. Articles by Haffty, B. G. Search for Related Content PubMed PubMed Citation Articles by Smith, B. D. Articles by Haffty, B. G. Social Bookmarking                            What's this?

Prognostic Significance of Vascular Endothelial Growth Factor Protein Levels in Oral and Oropharyngeal Squamous Cell Carcinoma

From the Departments of Therapeutic Radiology, Pathology, and Otolaryngology, Yale School of Medicine, New Haven, CT.

Address reprint requests to Bruce G. Haffty, MD, Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520-8040; email bruce.haffty{at}yale.edu

PURPOSE: Vascular Endothelial Growth Factor (VEGF) promotes angiogenesis in many different tumor types. VEGF levels may affect tumor growth, metastatic potential, and response to radiotherapy. This study assesses the prognostic value of VEGF protein levels in a cohort of patients with oral and oropharyngeal squamous cell carcinomas. The relationships between clinical outcome and the covariables of tumor-node-metastasis stage, disease stage (I to IV), grade, margin status, race, sex, and age were also determined.

PATIENTS AND METHODS: Chart review identified 77 patients with oral or oropharyngeal squamous cell carcinoma treated with gross total surgical resection and postoperative radiation between 1981 and 1992. Sufficient follow-up data and tumor tissue were available in 56 patients (73%). VEGF protein levels were determined using immunohistochemistry. The association between VEGF status, covariables, and outcome was assessed in a bivariate and multivariate model using two-sided statistical tests.

RESULTS: Twenty-three tumors (41%) were positive for VEGF expression. VEGF-positive tumors were more likely to recur locally (relative risk [RR] = 3.08; 95% confidence interval [CI], 1.03 to 9.24) and distantly (RR = 4.62; 95% CI, 1.41 to 15.10). In bivariate analysis, VEGF positivity was the most significant predictor of poor disease-free survival (RR = 2.66; 95% CI, 1.27 to 5.56) and overall survival (RR = 3.21; 95% CI, 1.63 to 6.32). In multivariate analysis, VEGF positivity was the most significant predictor of poor disease-free survival (RR = 2.75; 95% CI, 1.30 to 5.79) and overall survival (RR = 3.53; 95% CI, 1.75 to 7.13).

CONCLUSION: In this cohort, VEGF positivity was the most significant predictor of poor prognosis. VEGF status may prove to be an important prognostic factor in head and neck cancer.

Yale University School of Medicine Medical Student Research Training Fellowship, Yale Comprehensive Cancer Center Clinical Studies Support Award.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S. Shinriki, H. Jono, K. Ota, M. Ueda, M. Kudo, T. Ota, Y. Oike, M. Endo, M. Ibusuki, A. Hiraki, et al. Humanized Anti-Interleukin-6 Receptor Antibody Suppresses Tumor Angiogenesis and In vivo Growth of Human Oral Squamous Cell Carcinoma Clin. Cancer Res., September 1, 2009; 15(17): 5426 - 5434. [Abstract] [Full Text] [PDF]

				M. Kaya, T. Wada, S. Nagoya, M. Sasaki, T. Matsumura, and T. Yamashita The level of vascular endothelial growth factor as a predictor of a poor prognosis in osteosarcoma J Bone Joint Surg Br, June 1, 2009; 91-B(6): 784 - 788. [Abstract] [Full Text] [PDF]

				H. Schoder, M. Fury, N. Lee, and D. Kraus PET Monitoring of Therapy Response in Head and Neck Squamous Cell Carcinoma J. Nucl. Med., May 1, 2009; 50(Suppl_1): 74S - 88S. [Abstract] [Full Text] [PDF]

				D. Sano, S. Choi, Z. L. Milas, G. Zhou, C. E. Galer, Y.-W. Su, M. Gule, M. Zhao, Z. Zhu, and J. N. Myers The Effect of Combination Anti-Endothelial Growth Factor Receptor and Anti-Vascular Endothelial Growth Factor Receptor 2 Targeted Therapy on Lymph Node Metastasis: A Study in an Orthotopic Nude Mouse Model of Squamous Cell Carcinoma of the Oral Tongue Arch Otolaryngol Head Neck Surg, April 1, 2009; 135(4): 411 - 420. [Abstract] [Full Text] [PDF]

				T. Y. Seiwert, D. J. Haraf, E. E.W. Cohen, K. Stenson, M. E. Witt, A. Dekker, M. Kocherginsky, R. R. Weichselbaum, H. X. Chen, and E. E. Vokes Phase I Study of Bevacizumab Added to Fluorouracil- and Hydroxyurea-Based Concomitant Chemoradiotherapy for Poor-Prognosis Head and Neck Cancer J. Clin. Oncol., April 1, 2008; 26(10): 1732 - 1741. [Abstract] [Full Text] [PDF]

				S. Choi and J.N. Myers Molecular Pathogenesis of Oral Squamous Cell Carcinoma: Implications for Therapy Journal of Dental Research, January 1, 2008; 87(1): 14 - 32. [Abstract] [Full Text] [PDF]

				T. Kaneko, Z. Zhang, M. G. Mantellini, E. Karl, B. Zeitlin, M. Verhaegen, M. S. Soengas, M. Lingen, R. M. Strieter, G. Nunez, et al. Bcl-2 Orchestrates a Cross-talk between Endothelial and Tumor Cells that Promotes Tumor Growth Cancer Res., October 15, 2007; 67(20): 9685 - 9693. [Abstract] [Full Text] [PDF]

				N. Boku, A. Ohtsu, F. Nagashima, K. Shirao, and W. Koizumi Relationship between Expression of Vascular Endothelial Growth Factor in Tumor Tissue from Gastric Cancers and Chemotherapy Effects: Comparison between S-1 alone and the Combination of S-1 plus CDDP Jpn. J. Clin. Oncol., August 2, 2007; (2007) hym057v1. [Abstract] [Full Text] [PDF]

				N. Boku, A. Ohtsu, S. Yoshida, K. Shirao, Y. Shimada, I. Hyodo, H. Saito, Y. Miyata, and Gastrointestinal Oncology Study Group of Japan Cli Significance of Biological Markers for Predicting Prognosis and Selecting Chemotherapy Regimens of Advanced Gastric Cancer Patients between Continuous Infusion of 5-FU and a Combination of 5-FU and Cisplatin Jpn. J. Clin. Oncol., May 23, 2007; (2007) hym015v1. [Abstract] [Full Text] [PDF]

				M. K. Khan, F. Mamou, M. J. Schipper, K. S. May, A. Kwitny, A. Warnat, B. Bolton, B. M. Nair, M. S. T. Kariapper, M. Miller, et al. Combination tetrathiomolybdate and radiation therapy in a mouse model of head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg, March 1, 2006; 132(3): 333 - 338. [Abstract] [Full Text] [PDF]

				A. Celetti, D. Testa, S. Staibano, F. Merolla, V. Guarino, M. D. Castellone, R. Iovine, G. Mansueto, P. Somma, G. De Rosa, et al. Overexpression of the Cytokine Osteopontin Identifies Aggressive Laryngeal Squamous Cell Carcinomas and Enhances Carcinoma Cell Proliferation and Invasiveness Clin. Cancer Res., November 15, 2005; 11(22): 8019 - 8027. [Abstract] [Full Text] [PDF]

				J Lim, J-H Kim, J-Y Paeng, M-J Kim, S-D Hong, J-I Lee, and S-P Hong Prognostic value of activated Akt expression in oral squamous cell carcinoma J. Clin. Pathol., November 1, 2005; 58(11): 1199 - 1205. [Abstract] [Full Text] [PDF]

				X.-F. Zhu, B.-F. Xie, J.-M. Zhou, G.-K. Feng, Z.-C. Liu, X.-Y. Wei, F.-X. Zhang, M.-F. Liu, and Y.-X. Zeng Blockade of Vascular Endothelial Growth Factor Receptor Signal Pathway and Antitumor Activity of ON-III (2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone), a Component from Chinese Herbal Medicine Mol. Pharmacol., May 1, 2005; 67(5): 1444 - 1450. [Abstract] [Full Text] [PDF]

				S. Arora, J. Kaur, C. Sharma, M. Mathur, S. Bahadur, N. K. Shukla, S. V.S. Deo, and R. Ralhan Stromelysin 3, Ets-1, and Vascular Endothelial Growth Factor Expression in Oral Precancerous and Cancerous Lesions: Correlation with Microvessel Density, Progression, and Prognosis Clin. Cancer Res., March 15, 2005; 11(6): 2272 - 2284. [Abstract] [Full Text] [PDF]

				P. A. Kyzas, I. W. Cunha, and J. P.A. Ioannidis Prognostic Significance of Vascular Endothelial Growth Factor Immunohistochemical Expression in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis Clin. Cancer Res., February 15, 2005; 11(4): 1434 - 1440. [Abstract] [Full Text] [PDF]

				B. W. Chang, D. H. Kim, D. P. Kowalski, J. A. Burleson, Y. H. Son, L. D. Wilson, and B. G. Haffty Prognostic Significance of Cyclooxygenase-2 in Oropharyngeal Squamous Cell Carcinoma Clin. Cancer Res., March 1, 2004; 10(5): 1678 - 1684. [Abstract] [Full Text] [PDF]

				L. W. Chan, M. A. Moses, E. Goley, M. Sproull, T. Muanza, C. N. Coleman, W. D. Figg, P. S. Albert, C. Menard, and K. Camphausen Urinary VEGF and MMP Levels As Predictive Markers of 1-Year Progression-Free Survival in Cancer Patients Treated With Radiation Therapy: A Longitudinal Study of Protein Kinetics Throughout Tumor Progression and Therapy J. Clin. Oncol., February 1, 2004; 22(3): 499 - 506. [Abstract] [Full Text] [PDF]

				E. P. Hui, A. T. C. Chan, F. Pezzella, H. Turley, K.-F. To, T. C. W. Poon, B. Zee, F. Mo, P. M. L. Teo, D. P. Huang, et al. Coexpression of Hypoxia-inducible Factors 1{alpha} and 2{alpha}, Carbonic Anhydrase IX, and Vascular Endothelial Growth Factor in Nasopharyngeal Carcinoma and Relationship to Survival Clin. Cancer Res., August 1, 2002; 8(8): 2595 - 2604. [Abstract] [Full Text] [PDF]

				A. J. Khan, B. L. King, B. D. Smith, G. L. Smith, M. P. DiGiovanna, D. Carter, and B. G. Haffty Characterization of the HER-2/neu Oncogene by Immunohistochemical and Fluorescence in Situ Hybridization Analysis in Oral and Oropharyngeal Squamous Cell Carcinoma Clin. Cancer Res., February 1, 2002; 8(2): 540 - 548. [Abstract] [Full Text] [PDF]

				R. Masood, J. Cai, T. Zheng, D. L. Smith, D. R. Hinton, and P. S. Gill Vascular endothelial growth factor (VEGF) is an autocrine growth factor for VEGF receptor-positive human tumors Blood, September 15, 2001; 98(6): 1904 - 1913. [Abstract] [Full Text] [PDF]

				B. D. Smith, G. L. Smith, D. Carter, M. P. DiGiovanna, K. M. Kasowitz, C. T. Sasaki, and B. G. Haffty Molecular Marker Expression in Oral and Oropharyngeal Squamous Cell Carcinoma Arch Otolaryngol Head Neck Surg, July 1, 2001; 127(7): 780 - 785. [Abstract] [Full Text] [PDF]

				R. T.-P. Poon, S.-T. Fan, and J. Wong Clinical Implications of Circulating Angiogenic Factors in Cancer Patients J. Clin. Oncol., February 15, 2001; 19(4): 1207 - 1225. [Abstract] [Full Text] [PDF]