Expression and prognostic significance of a panel of tissue hypoxia markers in head-and-neck squamous cell carcinomas

Le, Quynh T., Kong, Christina, Lavori, Phillip W., O'Byrne, Kenneth J., Erler, Janine T., Huang, Xin, Chen, Yujin, Cao, Hongbin, Tibshirani, Robert, Denko, Nick, Giaccia, Amato J., & Koong, Albert C. (2007) Expression and prognostic significance of a panel of tissue hypoxia markers in head-and-neck squamous cell carcinomas. International Journal of Radiation Oncology Biology Physics, 69(1), pp. 167-175.

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Purpose: To investigate the expression pattern of hypoxia-induced proteins identified as being involved in malignant progression of head-and-neck squamous cell carcinoma (HNSCC) and to determine their relationship to tumor pO 2 and prognosis.

Methods and Materials: We performed immunohistochemical staining of hypoxia-induced proteins (carbonic anhydrase IX [CA IX], BNIP3L, connective tissue growth factor, osteopontin, ephrin A1, hypoxia inducible gene-2, dihydrofolate reductase, galectin-1, IκB kinase β, and lysyl oxidase) on tumor tissue arrays of 101 HNSCC patients with pretreatment pO 2 measurements. Analysis of variance and Fisher's exact tests were used to evaluate the relationship between marker expression, tumor pO 2, and CA IX staining. Cox proportional hazard model and log-rank tests were used to determine the relationship between markers and prognosis.

Results: Osteopontin expression correlated with tumor pO 2 (Eppendorf measurements) (p = 0.04). However, there was a strong correlation between lysyl oxidase, ephrin A1, and galectin-1 and CA IX staining. These markers also predicted for cancer-specific survival and overall survival on univariate analysis. A hypoxia score of 0-5 was assigned to each patient, on the basis of the presence of strong staining for these markers, whereby a higher score signifies increased marker expression. On multivariate analysis, increasing hypoxia score was an independent prognostic factor for cancer-specific survival (p = 0.015) and was borderline significant for overall survival (p = 0.057) when adjusted for other independent predictors of outcomes (hemoglobin and age).

Conclusions: We identified a panel of hypoxia-related tissue markers that correlates with treatment outcomes in HNSCC. Validation of these markers will be needed to determine their utility in identifying patients for hypoxia-targeted therapy. © 2007 Elsevier Inc. All rights reserved.

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ID Code: 65221
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: Head-and-neck cancer, Hypoxia, Marker panel, Prognosis, Marker panels, Cells, Enzyme activity, Growth kinetics, Histology, Immunology, Tissue, Biomarkers, carbonate dehydratase IX, connective tissue growth factor, dihydrofolate reductase, ephrin A1, galectin 1, hemoglobin, hypoxia inducible gene 2 protein, I kappa B kinase, osteopontin, protein, protein BNip3, protein lysine 6 oxidase, unclassified drug, adult, age, analysis of variance, article, cancer survival, controlled study, female, Fisher exact test, head and neck carcinoma, human, human tissue, log rank test, male, multivariate analysis, oxygen tension, priority journal, proportional hazards model, protein expression, squamous cell carcinoma, tissue microarray, univariate analysis, Antigens, Neoplasm, Carbonic Anhydrases, Carcinoma, Squamous Cell, Cell Hypoxia, Cell Line, Tumor, Disease Progression, Ephrin-A1, Head and Neck Neoplasms, Humans, I-kappa B Kinase, Membrane Proteins, Middle Aged, Neoplasm Proteins, Oxygen, Partial Pressure, Protein-Lysine 6-Oxidase, Proto-Oncogene Proteins, Tetrahydrofolate Dehydrogenase, Tumor Markers, Biological, Tumor Suppressor Proteins
DOI: 10.1016/j.ijrobp.2007.01.071
ISSN: 0360-3016
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2007 Elsevier Inc.
Deposited On: 09 Dec 2013 03:19
Last Modified: 11 Mar 2014 01:05

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