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Uttam K. Sinha, MD; Kashif Mazhar, MD; Steven B. Chinn, MS; Vaninder K. Dhillon, BS; Lihua Liu, PhD; Rizwan Masood, PhD; Dale H. Rice, MD; Parkash S. Gill, MD

Arch Otolaryngol Head Neck Surg. 2006;132:1053-1059.

Objective  To examine the expression of EphB4 in tumor tissue, surrounding normal tissue, and metastatic lymph node in patients with head and neck squamous cell carcinoma (HNSCC) and to evaluate its association with disease stage and smoking.

Design  A retrospective study.

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

Patients  Forty-eight patients with different stages of HNSCC (I-IV) were enrolled into this study. Staging was based on the staging system of the American Joint Committee on Cancer.

Main Outcome Measures  EphB4 expression in tumor tissue, surrounding normal tissue, and metastatic lymph node was evaluated by immunohistochemical analysis, Western blot, and real-time polymerase chain reaction. EphB4 expression was then compared between patients based on disease stage and smoking status.

Results  EphB4 expression was detected in all tumor specimens and metastatic lymph nodes of patients with HNSCC, but expression levels were higher in the metastatic lymph nodes. There was a statistically significantly higher mean EphB4 protein expression and EphB4 gene amplification in patients with advanced disease (stage III or IV) vs patients with initial disease (stage I or II) and in smokers vs nonsmokers.

Conclusions  Overexpression of EphB4 is associated with advanced stages of HNSCC as well as with patients who smoke. These data are the first to demonstrate the association of EphB4 with advanced stages of disease and smoking in HNSCC and hence provide a strong rationale for targeting EphB4 for HNSCC therapies.

Author Affiliations: Departments of Otolaryngology (Drs Sinha, Masood, and Rice, Mr Chinn, and Ms Dhillon), Preventive Medicine (Drs Mazhar and Liu), and Pathology (Drs Masood and Gill), Keck School of Medicine (Drs Sinha, Masood, Rice, and Gill, Mr Chinn, and Ms Dhillon), Center for Craniofacial Molecular Biology–School of Dentistry (Dr Sinha), and Norris Cancer Center (Drs Sinha and Gill), University of Southern California, Los Angeles.

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