title: Aberrant  beta-catenin and LEF1 expression may predict the clinical outcome for patients with oropharyngeal cancer.
abstract: Beta-catenin,  normally  expressed  on  the  epithelial  cell  surface,  plays  a crucial role in cadherin-mediated cell adhesion. Recent evidence suggests that beta-catenin is also involved in other functions such as intracellular signaling via the Wnt pathway by creating a nuclear complex with members of the Lymphoid-Enhancer-Factor/T-Cell-Factor (LEF/TCF) family of transcription  factors, and gene regulation that it is implicated in the development of several tumors. Little information is available on beta-catenin expression and its main partner in the Wnt signaling pathway, LEF1, in oropharyngeal squamous cell  carcinomas (OP-SCCs). The aim of this  study is to investigate the expression  of beta-catenin and LEF1 expression in human primary OP-SCCs and to evaluate their clinical and prognostic significance.  OP-SCCs and normal  peritumoral areas were analyzed by  immunohistochemistry, Western-blot and RT-PCR. Beta-catenin was overexpressed in tumors in comparison to normal peritumoral areas and displayed predominantly intracellular (cytosolic/nuclear) localization in 62&#x0025; of the tumors. Immunoreactivity was correlated with clinicopathological parameters and long-term follow-up, and a significant association was found between protein expression and development of local recurrences (P =0.03). The OP-SCCs with poor clinical outcome, which displayed intracellular beta-catenin expression, were also strongly positive for LEF1, with their co-expression statistically significant (P = 0.040). All (100&#x0025;) advanced (stages 3+4) SCCs, 66.7&#x0025; of the SCCs with positive lymph nodes and 80&#x0025; of the SSCs that developed local recurrences were LEF1 positive. Cox regression analysis confirmed a poorer overall survival in cases with high expression of beta-catenin and LEF1. Our results suggest that assessing intracellular beta-catenin and LEF1  expression might help in patient risk  stratification and outcome prediction, and serve as novel therapeutic targets in advanced OP-SCC.
authors.affiliation: Department of Orthodontics and Pediatric Dentistry, University of Michigan Ann Arbor, MI, USA. silvanap@umich.edu
authors.forename: P
authors.initials: P
authors.lastname: Papagerakis
authors.forename: G
authors.initials: G
authors.lastname: Pannone
authors.forename: A-H
authors.initials: AH
authors.lastname: Shabana
authors.forename: J
authors.initials: J
authors.lastname: Depondt
authors.forename: A
authors.initials: A
authors.lastname: Santoro
authors.forename: K
authors.initials: K
authors.lastname: Ghirtis
authors.forename: A
authors.initials: A
authors.lastname: Berdal
authors.forename: S
authors.initials: S
authors.lastname: Papagerakis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000032:analysis* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009959:Oropharyngeal Neoplasms / Q000737:chemistry* / Q000473:pathology; D011446:Prospective Studies; D051176:beta Catenin / Q000032:analysis* / Q000502:physiology
chemical_list: C495270:CTNNB1 protein, human; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; D051176:beta Catenin