title: Molecular markers predict outcome in squamous cell carcinoma of the head and neck after concomitant cisplatin-based chemoradiation.
abstract: Not all patients with squamous cell carcinomas of the head and neck (HNSCC) benefit from concurrent cisplatin-based chemoradiation, but reliable predictive markers for outcome after chemoradiation are scarce. We have investigated potential prognostic biomarkers for outcome in a large group of patients. Ninety-one tumor biopsies taken from consecutive HNSCC patients were evaluated for protein expression on a tissue microarray. Using immunohistochemistry, 18 biomarkers, involved in various cellular pathways were investigated. Univariable and multivariable proportional hazard analyses were performed to investigate associations between each individual marker and outcome. In addition, the global test was used to test all variables simultaneously and selected combinations of markers for an overall association with local control. Univariable analysis showed statistically significant increased relative risks of RB, P16 and MRP2 for local control and MDR1 and HIF-1alpha for overall survival. MRP2, MDR1 and P16 levels were positively associated with outcome whereas RB and HIF-1alpha had a negative relationship. Using Goeman's global testing no combination of markers was identified that was associated with local control. Grouping the markers according to their function revealed an association between a combination of 3 markers (P16, P21 and P27) and outcome (p = 0.05) was found. In the multivariable analysis, MRP2 and RB remained significant independent predictive markers for local control. This study describes the prognostic value of biomarkers for the outcome in patients uniformly treated with concurrent chemoradiation. MRP2 and RB were found to be associated with outcome in patients treated with concurrent chemoradiation.
authors.affiliation: Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. g.b.vandenbroek@amc.nl
authors.forename: Guido B
authors.initials: GB
authors.lastname: van den Broek
authors.forename: Maarten
authors.initials: M
authors.lastname: Wildeman
authors.forename: Coen R N
authors.initials: CR
authors.lastname: Rasch
authors.forename: Nicola
authors.initials: N
authors.lastname: Armstrong
authors.forename: Ed
authors.initials: E
authors.lastname: Schuuring
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Begg
authors.forename: Leendert H J
authors.initials: LH
authors.lastname: Looijenga
authors.forename: Rik
authors.initials: R
authors.lastname: Scheper
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: van der Wal
authors.forename: Lorian
authors.initials: L
authors.lastname: Menkema
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
authors.forename: Alfons J M
authors.initials: AJ
authors.lastname: Balm
authors.forename: Marie-Louise F
authors.initials: ML
authors.lastname: van Velthuysen
authors.forename: Michiel W M
authors.initials: MW
authors.lastname: van den Brekel
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000628:therapy*; D002945:Cisplatin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000628:therapy*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis; D015999:Multivariate Analysis; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016160:Retinoblastoma Protein / Q000032:analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D002945:Cisplatin; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016160:Retinoblastoma Protein; C000715087:ABCC2 protein, human; C497442:HIF1A protein, human