All work was conducted at the University of Michigan
Triological Society Candidate Thesis
Biomarkers in advanced larynx cancer
Article first published online: 12 JUL 2013
© 2013 The American Laryngological, Rhinological and Otological Society, Inc.
Volume 124, Issue 1, pages 179–187, January 2014
How to Cite
Bradford, C. R., Kumar, B., Bellile, E., Lee, J., Taylor, J., D'Silva, N., Cordell, K., Kleer, C., Kupfer, R., Kumar, P., Urba, S., Worden, F., Eisbruch, A., Wolf, G. T., Teknos, T. N., Prince, M. E.P., Chepeha, D. B., Hogikyan, N. D., Moyer, J. S. and Carey, T. E. (2014), Biomarkers in advanced larynx cancer. The Laryngoscope, 124: 179–187. doi: 10.1002/lary.24245
Presented at the Combined Triological Society Section Meetings, Miami, Florida, U.S.A., February 26–28, 2012.
Study supported by the University of Michigan Head and Neck Cancer SPORE (NCI P50 CA97248) and the University of Michigan Comprehensive Cancer Center Core Grant (NCI P30 CA46592). The authors have no other funding, financial relationships, or conflicts of interest to disclose.
- Issue published online: 20 DEC 2013
- Article first published online: 12 JUL 2013
- Accepted manuscript online: 18 JUN 2013 03:18AM EST
- Manuscript Accepted: 20 MAY 2013
- Manuscript Revised: 21 APR 2013
- Manuscript Received: 3 FEB 2013
- Laryngeal cancer or carcinoma;
- cyclin D1
To determine if tumor biomarkers were predictive of outcome in a prospective cohort of patients with advanced larynx cancer treated in a phase II clinical trial.
Prospectively collected biopsy specimens from 58 patients entered into a Phase II trial of organ preservation in advanced laryngeal cancer were evaluated for expression of a large panel of biomarkers, and correlations with outcome were determined.
Tissue microarrays were constructed from pretreatment biopsies and stained for cyclin D1, CD24, EGFR, MDM2, PCNA, p53, survivin, Bcl-xL, Bcl-2, BAK, rhoC, and NFκB. Pattern of invasion and p53 mutations were assessed. Correlations with overall survival (OS), disease-specific survival (DSS), time free from indication of surgery, induction chemotherapy response, and chemoradiation response were determined. Cox models were used to assess combinations of these biomarkers.
Low expression of BAK was associated with response to induction chemotherapy. Low expression of BAK and cytoplasmic NFκB was associated with chemoradiation response. Aggressive histologic growth pattern was associated with response induction chemotherapy. Expression of cyclin D1 was predictive of overall and disease-specific survival. Overexpression of EGFR was also associated with an increased risk of death from disease. Bcl-xL expression increased significantly in persistent/recurrent tumors specimens when compared to pretreatment specimens derived from the same patient (P = 0.0003).
Evaluation of biomarker expression in pretreatment biopsy specimens can lend important predictive and prognostic information for patients with advanced larynx cancer.
Level of Evidence
N/A. Laryngoscope, 124:179–187, 2014