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Eric J. Yavrouian, MD; Uttam K. Sinha, MD; Dale H. Rice, MD; Muhammad T. Salam, MBBS, MS; Parkash S. Gill, MD; Rizwan Masood, PhD

Arch Otolaryngol Head Neck Surg. 2008;134(9):985-991.

Objectives  To examine the expression of EphB4 and EphrinB2 in tumor tissue and surrounding normal tissue in patients with head and neck squamous cell carcinoma (HNSCC) and to evaluate its association with overall patient survival.

Design  Retrospective study.

Setting  University of Southern California–University Hospital, the Los Angeles County and University of Southern California Medical Center, and the Department of Otolaryngology–Head and Neck Surgery, University of Southern California, Los Angeles.

Patients  Fifty patients, 8 with early-stage (stages I and II) and 42 with advanced-stage (stages III and IV) HNSCC, were enrolled into this study. Staging was based on the system of the American Joint Committee on Cancer.

Main Outcome Measures  EphB4 and EphrinB2 expression was evaluated by Western blot analysis. Overall survival in patients was then compared with EphB4 and EphrinB2 expression.

Results  EphB4 and EphrinB2 expression was detected in all normal and tumor samples in patients with HNSCC, with the magnitude of EphB4 overexpression greater than that of EphrinB2 expression compared with normal tissue. There was a statistically significant decrease in overall survival among patients with elevated EphB4 and EphrinB2 expression (P < .001).

Conclusions  EphB4 and EphrinB2 overexpression is associated with poor overall survival in patients with HNSCC. Our results are the first to demonstrate an association between decreased survival and elevated expression of the receptor tyrosine kinase EphB4 and its ligand EphrinB2, suggesting that EphB4 and EphrinB2 may be used as biomarkers to predict prognosis and as targets in future HNSCC therapies.

Author Affiliations: Departments of Otolaryngology–Head and Neck Surgery (Drs Yavrouian, Sinha, Rice, and Masood), Preventive Medicine (Dr Salam), and Pathology (Drs Gill and Masood), Keck School of Medicine, Center for Craniofacial Molecular Biology, School of Dentistry (Dr Sinha), and Norris Cancer Center (Drs Sinha and Gill), University of Southern California, Los Angeles.