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PURPOSE: To validate lysyl oxidase (LOX), a hypoxia-related protein, as a marker for metastasis in an independent head and neck cancer (HNC) patient group enrolled onto a prospective trial. PATIENTS AND METHODS: We performed traditional immunohistochemical (IHC) staining and automated quantitative analysis (AQUA) for LOX expression in 66 HNC patients from one institution. We also performed AQUA staining for LOX in 306 of 1,113 patients treated on a phase III trial comparing four radiation fractionation schedules in locally advanced HNC (RTOG 90-03). Pretreatment characteristics and outcome were similar between patients with and without LOX assessment. We correlated AQUA LOX expression with time to metastasis (TTM), time to progression (TTP), and overall survival (OS). RESULTS: LOX expression from both staining methods predicted for TTM in the first 66 patients. Multivariate analysis, controlling for significant parameters including nodal stage and performance status, revealed tumor LOX expression, as a continuous variable, was an independent predictor for TTM (hazard ratio [HR], 1.21; 95% CI, 1.10 to 1.33; P = .0001), TTP (HR, 1.06; 95% CI, 1.02 to 1.10; P = .0069), and OS (HR, 1.04; 95% CI, 1.00 to 1.07; P = .0311) in RTOG 90-03 patients. This translates into a 259% increase in metastatic risk for a patient at the 75th percentile of LOX compared with one at the 25th percentile. CONCLUSION: AQUA LOX expression was strongly associated with increased metastasis, progression, and death in RTOG 90-03 patients. This study validates that LOX is a marker for metastasis and survival in HNC.

Original publication

DOI

10.1200/JCO.2008.20.6003

Type

Journal article

Journal

J Clin Oncol

Publication Date

10/09/2009

Volume

27

Pages

4281 - 4286

Keywords

Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Carcinoma, Squamous Cell, Cause of Death, Disease Progression, Female, Head and Neck Neoplasms, Humans, Immunohistochemistry, Male, Middle Aged, Multivariate Analysis, Neoplasm Metastasis, Prognosis, Proportional Hazards Models, Protein-Lysine 6-Oxidase, Reproducibility of Results, Sensitivity and Specificity, Staining and Labeling, Survival Analysis, Survival Rate