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ß-Catenin Functions Mainly as an Adhesion Molecule in Patients with Squamous Cell Cancer of the Head and Neck

Authors' Affiliation: Departments of ¹ Otolaryngology, ² Pathology, ³ Radiation Therapy, and ⁴ Internal Medicine, Yale University School of Medicine, New Haven, Connecticut

Requests for reprints: Amanda Psyrri, Department of Medical Oncology, Yale University School of Medicine, New Haven, CT 06514. Phone: 203-737-2476; Fax: 203-785-7531; E-mail: diamando.psyrri{at}yale.edu.

Background: ß-catenin, depending on subcellular localization, plays a dual role in carcinogenesis: as a signaling factor (in the nucleus) and as an adhesion molecule (in cell membrane). In this study, we sought to determine the role of ß-catenin in head and neck carcinogenesis.

Methods: First, we studied the incidence of mutations of ß-catenin in a cohort of 60 head and neck squamous cell cancers (HNSCC). We subsequently evaluated the protein expression levels of ß-catenin in a cohort of oropharyngeal squamous cell cancer tissue microarray using a novel in situ method of quantitative protein analysis and correlated those with cyclin D1 levels and clinical and pathologic data.

Results: The mean follow-up time for survivors was 45 months and for all patients was 35 months. We found no mutations in the cohort of 60 HNSCC. ß-catenin displayed primarily membranous expression pattern. Patients with high tumor-node-metastasis stage were more likely to have high expression of ß-catenin (P = 0.040). Patients with low ß-catenin expression had a local recurrence rate of 79% compared with 29% for patients with high ß-catenin tumors (P = 0.0021). Univariate Cox regression revealed a hazard ratio for low ß-catenin tumors of 3.6 (P = 0.004). Kaplan-Meier analysis showed that patients with low ß-catenin expressing tumors trended toward worse 5-year disease-free survival (P = 0.06). In multivariate analysis, only ß-catenin expression status was an independent prognostic factor (P = 0.044) for local recurrence. Tumors with high ß-catenin had low cyclin D1 and vice versa (P = 0.007).

Conclusions: The absence of activating ß-catenin mutations combined with the inverse correlation between ß-catenin levels with cyclin D1 levels and outcome suggest that ß-catenin mainly functions as an adhesion and not signaling molecule in HNSCC.

Key Words: Head and neck/oral cancers • Carcinoginesis • Cell adhesion • Risk assessment

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