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Molecular Profiling of Tumor Progression in Head and Neck Cancer
Thomas J. Belbin, PhD;
Bhuvanesh Singh, MD;
Richard V. Smith, MD;
Nicholas D. Socci, PhD;
Volkert B. Wreesmann, PhD;
Marta Sanchez-Carbayo, PhD;
Jessica Masterson, MD;
Snehal Patel, MD;
Carlos Cordon-Cardo, MD, PhD;
Michael B. Prystowsky, MD, PhD;
Geoffrey Childs, PhD
Arch Otolaryngol Head Neck Surg. 2005;131:10-18.
Objective To assess gene expression changes associated with tumor progression in patients with squamous cell carcinoma of the oral cavity.
Design A microarray containing 17 840 complementary DNA clones was used to measure gene expression changes associated with tumor progression in 9 patients with squamous cell carcinoma of the oral cavity. Samples were taken for analysis from the primary tumor, nodal metastasis, and "normal" mucosa from the patients’ oral cavity.
Setting Tertiary care facility.
Patients Nine patients with stage III or stage IV untreated oral cavity squamous cell carcinoma.
Results Our analysis to categorize genes based on their expression patterns has identified 140 genes that consistently increased in expression during progression from normal tissue to invasive tumor and subsequently to metastatic node (in at least 4 of the 9 cases studied). A similar list of 94 genes has been identified that decreased in expression during tumor progression and metastasis. We validated this gene discovery approach by selecting moesin (a member of the ezrin/radixin/moesin [ERM] family of cytoskeletal proteins) and one of the genes that consistently increased in expression during tumor progression for subsequent immunohistochemical analysis using a head and neck squamous cell carcinoma tissue array.
Conclusion A distinct pattern of gene expression, with progressive up- or down-regulation of expression, is found during the progression from histologically normal tissue to primary carcinoma and to nodal metastasis.
Author Affiliations: Departments of Pathology (Drs Belbin, Socci, Masterson, and Prystowsky) and Molecular Genetics (Dr Childs) and Seaver Center for Computational Biology (Dr Socci), Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY; Laboratory of Epithelial Cancer Biology, Head and Neck Service (Drs Singh, Wreesmann, and Patel) and Department of Molecular Pathology (Drs Sanchez-Carbayo and Cordon-Cardo), Memorial Sloan-Kettering Cancer Center, New York, NY; and Department of Otolaryngology, Montefiore Medical Center, Medical Arts Pavilion, Bronx (Dr Smith).
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