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Hideaki Tsuzuki, MD; Hiroshi Sunaga, MD; Toshihisa Ito, MD; Norihiko Narita, MD; Chizuru Sugimoto, MD; Shigeharu Fujieda, MD

Arch Otolaryngol Head Neck Surg. 2005;131:1071-1078.

Objective  To identify a strong prognostic biological marker for patients with oral and oropharyngeal squamous cell carcinomas.

Design  We evaluated the protein expressions of 26 tumor-associated factors, including cytokines and cytokine receptors (granulocyte colony-stimulating factor [G-CSF], interleukin 10 [IL-10], G-CSF receptor [G-CSFR], and IL-12 receptor); angiogenic factors (platelet-derived endothelial cell growth factor [PD-ECGF] and vessel count); cell cycle–related proteins (p27, cyclin D1, and cyclin E); apoptosis-related factors (wild-type p53, Bax, Bcl-2, apoptotic index, Fas, and Fas ligand); oncogene proteins (c-fos and c-Myc); cell-surface proteins (P-glycoprotein, multidrug resistance–associated protein, nm23, and CD40); intracellular proteins (aryl hydrocarbon receptor nuclear translocator, aryl hydrocarbon receptor, and heat shock protein 27); and DNA mismatch-repair genes (protein encoded by human mutL homologue 1 and the human mutS homologue of the chromosome 2p gene) by means of immunohistochemical analysis.

Setting  Department of Otorhinolaryngology—Head and Neck Surgery, University of Fukui, Fukui, Japan.

Patients  Fifty-eight patients who underwent surgical resections of oral and oropharyngeal squamous cell carcinomas.

Results  A low-level PD-ECGF expression, a hypovascular count, or a low-level G-CSFR expression was associated with a favorable clinical outcome using the Kaplan-Meier method. Univariate analysis showed that PD-ECGF expression (odds, 4.19; P = .02), G-CSFR expression (odds, 4.10; P = .01), and vessel count (odds, 2.80; P = .04) had significant hazard rates. When multivariate analysis was performed on 6 factors, including sex, tumor size, lymph node metastasis, PD-ECGF expression, G-CSFR expression, and vessel count, patients with a positive expression of PD-ECGF had the highest relative risk value for death due to the disease (odds, 4.94; P = .01). Also, G-CSFR was an independent prognostic indicator in the model (odds, 3.29; P = .04). No correlations between other factors and prognoses were detected.

Conclusion  Expression of PD-ECGF was the most effective marker for making prognoses for oral and oropharyngeal squamous cell carcinomas, and G-CSFR expression was the second most effective among 26 tumor-associated factors.

Author Affiliations: Department of Otorhinolaryngology–Head and Neck Surgery, School of Medicine, University of Fukui, Fukui, Japan.

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