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...cervical nodes. Our goal was to determine if EphB4 is aberrantly expressed in cases of HNSCC and to determine if there is a qualitative difference between the expression of EphB4 on primary and metastatic tumors and its expression on normal mucosa adjacent to primary tumors. From each patient, we obtained specimens of the primary tumor, the nodal metastasis, and the adjacent normal mucosa, and we performed immunocytochemistry on each. We observed EphB4 expression in all primary and metastatic tumors and no expression in the normal tissue. In each of the six patients, expression was greater in the metastatic tumor than in the primary tumor. We conclude that EphB4 is a novel target in the treatment of HNSCC.
Introduction
Squamous cell carcinoma, the most common cancer of the head and neck, is caused primarily by tobacco-derived carcinogens. (1) Head and neck squamous cell carcinoma (HNSCC) has been shown to progress through a series of dysplastic histopathologic changes before it becomes an invasive cancer. The differences seen in normal epithelium in the upper aerodigestive tract and in cancer cells that arise from that tissue are the result of mutations in specific genes and alterations of their expression. (2) These genes control a variety of cellular processes, including proliferation and immortalization. Both the activation of oncogenes and the inactivation of tumor suppressor proteins are involved in these pathways.
Receptor tyrosine kinases have been widely implicated in the generation and progression of common human tumors, including HNSCC. (3) One of these kinases is the epidermal growth factor (EGF) receptor (EGFR) gene, which encodes a transmembrane receptor for EGF-family ligands. In HNSCC, EGFR and/or EGF ligand are over-expressed. (4,5)
The largest subfamily of receptor tyrosine kinases is the Eph family, which has 14 fully sequenced members. (6) The prototype of this gene family (EphA1) was isolated from an erythropoietin-producing hepatoma cell line. Initially, the ligands for these receptors were unknown, but they have since been identified. The...
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