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Imaging, Diagnosis, Prognosis |
Departments of 1 Otolaryngology, 2 Therapeutic Radiology, 3 Medical Oncology, 4 Pathology and 5 Biostatistics, Yale University School of Medicine, New Haven, Connecticut
Requests for reprints: Amanda Psyrri, Yale Cancer Center, P.O. Box 208032, New Haven, CT 06520. Phone: 203-737-2476; Fax: 203-785-7531; E-mail: diamando.psyrri{at}yale.edu.
Background: The current tumor-node-metastasis system is inadequate to accurately classify patients in terms of prognosis. Thus, with the availability of recently developed molecular tools, considerable interest lies in discovering prognostic markers in order to guide treatment decisions. In this study, we sought to determine the prognostic significance of the cell cycle regulator cyclin D1 in oropharyngeal squamous cell carcinoma (OSCC).
Experimental Design: We studied the protein expression levels of cyclin D1 on a tissue microarray composed of 63 OSCCs with long-term follow-up data available. Protein expression was analyzed with an automated in situ quantitative (AQUA) method which allows preservation of tissue morphology while quantifying protein expression in paraffin-embedded tissue.
Results: The mean follow-up time was 35 months. High cyclin D1 nuclear expression was associated with increased 5-year local recurrence rate (48% versus 15%), inferior 5-year disease-free survival (16% versus 58%), and inferior 5-year overall survival (17% versus 53%). In multivariate Cox regression, high nuclear cyclin D1 expression was an independent predictor for local recurrence, disease-free survival, and overall survival at 5 years.
Conclusions: Our results indicate that quantitative assessment of nuclear cyclin D1 expression level by automated in situ quantitative analysis is a strong predictor for outcome in OSCC. Thus, cyclin D1 may be a potential target for molecular intervention in patients with oropharyngeal squamous cell cancer.
Key Words: Head and neck cancer • Cell cycle checkpoints • Risk assessment • Proteomics
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