beta-Catenin functions mainly as an adhesion molecule in patients with squamous cell cancer of the head and neck.
BACKGROUND
beta-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 beta-catenin in head and neck carcinogenesis.


METHODS
First, we studied the incidence of mutations of beta-catenin in a cohort of 60 head and neck squamous cell cancers (HNSCC). We subsequently evaluated the protein expression levels of beta-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. beta-catenin displayed primarily membranous expression pattern. Patients with high tumor-node-metastasis stage were more likely to have high expression of beta-catenin (P = 0.040). Patients with low beta-catenin expression had a local recurrence rate of 79% compared with 29% for patients with high beta-catenin tumors (P = 0.0021). Univariate Cox regression revealed a hazard ratio for low beta-catenin tumors of 3.6 (P = 0.004). Kaplan-Meier analysis showed that patients with low beta-catenin expressing tumors trended toward worse 5-year disease-free survival (P = 0.06). In multivariate analysis, only beta-catenin expression status was an independent prognostic factor (P = 0.044) for local recurrence. Tumors with high beta-catenin had low cyclin D1 and vice versa (P = 0.007).


CONCLUSIONS
The absence of activating beta-catenin mutations combined with the inverse correlation between beta-catenin levels with cyclin D1 levels and outcome suggest that beta-catenin mainly functions as an adhesion and not signaling molecule in HNSCC.
Yu
Ziwei
Z
Department of Otolaryngology, Yale University School of Medicine, New Haven, Connecticut 06514, USA.
Weinberger
Paul M
PM
Provost
Elayne
E
Haffty
Bruce G
BG
Sasaki
Clarence
C
Joe
J
J
Camp
R L
RL
Rimm
D L
DL
Psyrri
Amanda
A
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D019938:Cyclin D1 / Q000032:analysis; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D004252:DNA Mutational Analysis; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009367:Neoplasm Staging; D016019:Survival Analysis; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D019938:Cyclin D1