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Molecular Profiling and the Identification of Genes Associated With Metastatic Oral Cavity/Pharynx Squamous Cell Carcinoma
Cecelia E. Schmalbach, MD, MS;
Douglas B. Chepeha, MD, MSPH;
Thomas J. Giordano, MD, PhD;
Mark A. Rubin, MD;
Theodoros N. Teknos, MD;
Carol R. Bradford, MD;
Gregory T. Wolf, MD;
Rork Kuick, MS;
David E. Misek, PhD;
Douglas K. Trask, MD, PhD;
Samir Hanash, MD, PhD
Arch Otolaryngol Head Neck Surg. 2004;130:295-302.
Objective To investigate differences in gene expression profiles between oral cavity/oropharynx squamous cell carcinoma (OC/OP SCC) primary tumors that have metastasized to cervical lymph nodes and nonmetastatic OC/OP SCC tumors.
Design Oligonucleotide microarray analysis of primary tumors was used to produce gene expression profiles. Profile comparisons between metastatic and nonmetastatic tumors were performed using principal component analysis, t test, and fold change differences. A similar comparison between metastatic tumors and noncancer oral mucosa samples was performed to ensure tumor origin.
Subjects A prospective cohort of 20 patients with previously untreated OC/OP SCC who underwent pathologic staging following surgical resection and lymphadenectomy.
Results Of the approximately 9600 genes profiled, 101 demonstrated significant expression differences between the metastatic and nonmetastatic tumors (fold change  1.5; P<.01). Among this subset, 57 genes also exhibited significant differences between metastatic tumors and normal mucosa samples (fold change 1.5; P<.05). This profile included genes related to the extracellular matrix, adhesion, motility, inflammation, and protease inhibition. Collagen type 11  -1 (COL11A1) demonstrated the greatest differential expression between metastatic and nonmetastatic OC/OP SCC tumors (fold change = 7.61; P = .002). Tissue inhibitor of metalloproteinase 1 (TIMP-1) also demonstrated increased expression in metastatic tumors (fold change = 3.3; P = .003).
Conclusions Metastatic OC/OP SCC has a distinct gene expression profile compared with nonmetastatic OC/OP SCC and normal oral mucosa. This metastatic profile includes genes related to the extracellular matrix, adhesion, motility, and protease inhibition. Knowledge gained through tumor gene expression profiling may facilitate early detection of aggressive tumors and targeted therapeutic interventions.
From the Departments of Otolaryngology–Head and Neck Surgery (Drs Schmalbach, Chepeha, Teknos, Bradford, and Wolf), Pathology (Drs Giordano and Rubin), and Pediatrics (Mr Kuick and Drs Misek and Hanash), University of Michigan Medical School, Ann Arbor; and Department of Otolaryngology–Head and Neck Surgery, University of Iowa, Iowa City (Dr Trask). The authors have no relevant financial interest in this article.
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