β-Catenin functions mainly as an adhesion molecule in patients with squamous cell cancer of the head and neck

Ziwei Yu, Paul M. Weinberger, Elayne Provost, Bruce G. Haffty, Clarence Sasaki, J. Joe, R. L. Camp, D. L. Rimm, Amanda Psyrri

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Background: β-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 β-catenin in head and neck carcinogenesis. Methods: First, we studied the incidence of mutations of β-catenin in a cohort of 60 head and neck squamous cell cancers (HNSCC). We subsequently evaluated the protein expression levels of β-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. β-catenin displayed primarily membranous expression pattern. Patients with high tumor-node-metastasis stage were more likely to have high expression of β-catenin (P = 0.040). Patients with low β-catenin expression had a local recurrence rate of 79% compared with 29% for patients with high β-catenin tumors (P = 0.0021). Univariate Cox regression revealed a hazard ratio for low β-catenin tumors of 3.6 (P = 0.004). Kaplan-Meier analysis showed that patients with low β-catenin expressing tumors trended toward worse 5-year disease-free survival (P = 0.06). In multivariate analysis, only β-catenin expression status was an independent prognostic factor (P = 0.044) for local recurrence. Tumors with high β-catenin had low cyclin D1 and vice versa (P = 0.007). Conclusions:The absence of activating β-catenin mutations combined with the inverse correlation between β-catenin levels with cyclin D1 levels and outcome suggest that β-catenin mainly functions as an adhesion and not signaling molecule in HNSCC.

Original languageEnglish (US)
Pages (from-to)2471-2477
Number of pages7
JournalClinical Cancer Research
Volume11
Issue number7
DOIs
StatePublished - Apr 1 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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