Molecular markers predict outcome in squamous cell carcinoma of the head and neck after concomitant cisplatin-based chemoradiation

Guido B van den Broek; Maarten Wildeman; Coen R N Rasch; Nicola Armstrong; Ed Schuuring; Adrian C Begg; Leendert H J Looijenga; Rik Scheper; Jacqueline E van der Wal; Lorian Menkema; Paul J van Diest; Alfons J M Balm; Marie-Louise F van Velthuysen; Michiel W M van den Brekel

doi:10.1002/ijc.24254

Molecular markers predict outcome in squamous cell carcinoma of the head and neck after concomitant cisplatin-based chemoradiation

Guido B van den Broek, Maarten Wildeman, Coen R N Rasch, Nicola Armstrong, Ed Schuuring, Adrian C Begg, Leendert H J Looijenga, Rik Scheper, Jacqueline E van der Wal, Lorian Menkema, Paul J van Diest, Alfons J M Balm, Marie-Louise F van Velthuysen, Michiel W M van den Brekel

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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.

Original language	English
Pages (from-to)	2643-50
Number of pages	8
Journal	International journal of cancer
Volume	124
Issue number	11
DOIs	https://doi.org/10.1002/ijc.24254
Publication status	Published - 1 Jun 2009
Externally published	Yes

Keywords

Adult
Aged
Biomarkers, Tumor/analysis
Carcinoma, Squamous Cell/mortality
Cisplatin/therapeutic use
Combined Modality Therapy
Female
Head and Neck Neoplasms/mortality
Humans
Hypoxia-Inducible Factor 1, alpha Subunit/analysis
Immunohistochemistry
Male
Middle Aged
Multidrug Resistance-Associated Protein 2
Multidrug Resistance-Associated Proteins/analysis
Multivariate Analysis
Prognosis
Proto-Oncogene Proteins c-bcl-2/analysis
Retinoblastoma Protein/analysis
Treatment Outcome

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10.1002/ijc.24254

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van den Broek, G. B., Wildeman, M., Rasch, C. R. N., Armstrong, N., Schuuring, E., Begg, A. C., Looijenga, L. H. J., Scheper, R., van der Wal, J. E., Menkema, L., van Diest, P. J., Balm, A. J. M., van Velthuysen, M.-L. F., & van den Brekel, M. W. M. (2009). Molecular markers predict outcome in squamous cell carcinoma of the head and neck after concomitant cisplatin-based chemoradiation. International journal of cancer, 124(11), 2643-50. https://doi.org/10.1002/ijc.24254

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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.",

keywords = "Adult, Aged, Biomarkers, Tumor/analysis, Carcinoma, Squamous Cell/mortality, Cisplatin/therapeutic use, Combined Modality Therapy, Female, Head and Neck Neoplasms/mortality, Humans, Hypoxia-Inducible Factor 1, alpha Subunit/analysis, Immunohistochemistry, Male, Middle Aged, Multidrug Resistance-Associated Protein 2, Multidrug Resistance-Associated Proteins/analysis, Multivariate Analysis, Prognosis, Proto-Oncogene Proteins c-bcl-2/analysis, Retinoblastoma Protein/analysis, Treatment Outcome",

author = "{van den Broek}, {Guido B} and Maarten Wildeman and Rasch, {Coen R N} and Nicola Armstrong and Ed Schuuring and Begg, {Adrian C} and Looijenga, {Leendert H J} and Rik Scheper and {van der Wal}, {Jacqueline E} and Lorian Menkema and {van Diest}, {Paul J} and Balm, {Alfons J M} and {van Velthuysen}, {Marie-Louise F} and {van den Brekel}, {Michiel W M}",

year = "2009",

month = jun,

day = "1",

doi = "10.1002/ijc.24254",

language = "English",

volume = "124",

pages = "2643--50",

journal = "International journal of cancer",

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publisher = "John Wiley and Sons Inc.",

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van den Broek, GB, Wildeman, M, Rasch, CRN, Armstrong, N, Schuuring, E, Begg, AC, Looijenga, LHJ, Scheper, R, van der Wal, JE, Menkema, L, van Diest, PJ, Balm, AJM, van Velthuysen, M-LF & van den Brekel, MWM 2009, 'Molecular markers predict outcome in squamous cell carcinoma of the head and neck after concomitant cisplatin-based chemoradiation', International journal of cancer, vol. 124, no. 11, pp. 2643-50. https://doi.org/10.1002/ijc.24254

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

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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 -

Molecular markers predict outcome in squamous cell carcinoma of the head and neck after concomitant cisplatin-based chemoradiation

Abstract

Keywords

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