TY - JOUR
T1 - Molecular markers predict outcome in squamous cell carcinoma of the head and neck after concomitant cisplatin-based chemoradiation
AU - van den Broek, Guido B
AU - Wildeman, Maarten
AU - Rasch, Coen R N
AU - Armstrong, Nicola
AU - Schuuring, Ed
AU - Begg, Adrian C
AU - Looijenga, Leendert H J
AU - Scheper, Rik
AU - van der Wal, Jacqueline E
AU - Menkema, Lorian
AU - van Diest, Paul J
AU - Balm, Alfons J M
AU - van Velthuysen, Marie-Louise F
AU - van den Brekel, Michiel W M
PY - 2009/6/1
Y1 - 2009/6/1
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Biomarkers, Tumor/analysis
KW - Carcinoma, Squamous Cell/mortality
KW - Cisplatin/therapeutic use
KW - Combined Modality Therapy
KW - Female
KW - Head and Neck Neoplasms/mortality
KW - Humans
KW - Hypoxia-Inducible Factor 1, alpha Subunit/analysis
KW - Immunohistochemistry
KW - Male
KW - Middle Aged
KW - Multidrug Resistance-Associated Protein 2
KW - Multidrug Resistance-Associated Proteins/analysis
KW - Multivariate Analysis
KW - Prognosis
KW - Proto-Oncogene Proteins c-bcl-2/analysis
KW - Retinoblastoma Protein/analysis
KW - Treatment Outcome
UR - http://www.scopus.com/inward/record.url?scp=64249088367&partnerID=8YFLogxK
U2 - 10.1002/ijc.24254
DO - 10.1002/ijc.24254
M3 - Article
C2 - 19253368
SN - 0020-7136
VL - 124
SP - 2643
EP - 2650
JO - International journal of cancer
JF - International journal of cancer
IS - 11
ER -