title: beta-Catenin, Nf-kappaB and FAS protein expression are independent events in head and neck cancer: study of their association with clinical parameters.
abstract: In spite of much effort, no good markers have yet been found for predicting prognosis or response to therapy in advanced head and neck squamous cell carcinoma (HNSCCs) patients. beta-catenin, a protein involved in the cytoskeleton, cell-cell adhesion and gene transcription, is a factor associated with tumour progression. Recently, an interaction has been reported between beta-catenin, and NF-kappaB coupled with an inverse association of beta-catenin, and FAS (CD95/APO-1) protein expression in breast and colorectal tumours. To confirm these observations and to test their clinical impact in HNSCCs we have evaluated the expression of beta-catenin, NF-kappaB and FAS proteins. We used tissue microarrays to simultaneously analyse the levels of these proteins immunohistochemically in 118 HNSCCs. Among the 113 tumours evaluable for beta-catenin, increased and decreased levels were detected in 41 (36%) and 62 (55%) of the tumours, respectively. beta-catenin, protein staining was mainly membranous but 10 tumours (9%) showed the clear presence of protein in the cytoplasm, and none in the nucleus. Moreover, 81% of the tumours had decreased FAS protein expression, indicating that loss of FAS protein is a common feature of HNSCCs. Abnormal or nuclear NF-kappaB staining was observed in 24% of the tumours. No association was detected between the expression levels of the proteins evaluated. Regarding clinical associations, tumours from the hypopharynx had significantly lower levels of beta-catenin expression than those from other locations (P<0.05). Moreover, our data revealed that patients whose tumours had low levels of beta-catenin protein expression had decreased survival probability (24.8 months vs. NR, P=0.03) and reduced response to therapy (15.4 vs. 43 months; P=0.01) compared with patients whose tumours had high levels of beta-catenin. Taken together, our observations indicate that beta-catenin, NF-kappaB and FAS expression are independent events during HNSCC development and that levels of beta-catenin protein may identify subsets of advanced HNSCCs patients with different prognosis and response to therapy capabilities.
authors.affiliation: Molecular Pathology Program, Spanish National Cancer Centre (CNIO), C/Melchor Fernandez Almagro, 3, 28029 Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Rodriguez-Pinilla
authors.forename: J L
authors.initials: JL
authors.lastname: Rodriguez-Peralto
authors.forename: R
authors.initials: R
authors.lastname: Hitt
authors.forename: J J
authors.initials: JJ
authors.lastname: Sanchez
authors.forename: L
authors.initials: L
authors.lastname: Sanchez-Verde
authors.forename: F
authors.initials: F
authors.lastname: Alameda
authors.forename: C
authors.initials: C
authors.lastname: Ballestin
authors.forename: M
authors.initials: M
authors.lastname: Sanchez-Cespedes
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000503:physiopathology*; D020869:Gene Expression Profiling; D006258:Head and Neck Neoplasms / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D016328:NF-kappa B / Q000032:analysis / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000096:biosynthesis*; D016019:Survival Analysis; D051176:beta Catenin / Q000032:analysis / Q000096:biosynthesis*; D019014:fas Receptor
chemical_list: D014408:Biomarkers, Tumor; C491901:FAS protein, human; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D051176:beta Catenin; D019014:fas Receptor