High Stromal Carbonic Anhydrase IX Expression Is Associated With Decreased Survival in p16-Negative Head-and-Neck Tumors
- Department of Population Health Research, Alberta Health Services-Cancer Care, Calgary, Alberta (Canada)
- Department of Oncology, University of Calgary, Calgary, Alberta (Canada)
- Department of Pathology, University of Calgary, Calgary, Alberta (Canada)
Purpose: Head-and-neck squamous cell carcinoma (HNSCC) is the fifth most common malignancy worldwide. Alcohol use and tobacco use are the most established risk factors; however, human papilloma virus (HPV) infection is a major risk factor for a subset of HNSCCs. Although HPV-positive tumors typically present at a more advanced stage at diagnosis, they are associated with a better prognosis. Tumor hypoxia confers poor prognosis and treatment failure, but direct tumor oxygen measurement is challenging. Endogenous markers of hypoxia (EMHs) have been proposed but have not replicated the prognostic utility of direct oxygen measurement. The expression of endogenous markers of hypoxia may be influenced by oxygen-independent factors, such as the HPV status of the tumor. Methods and Materials: Consecutive cases of locally advanced HNSCC, treated with a uniform regimen of combined radiotherapy and chemotherapy, were identified. Tissue microarrays were assembled from triplicate 0.6-mm cores of archived tumor tissue. HPV status was inferred from semiquantitative p16 immunostaining and directly measured by use of HPV-specific chromogenic in situ hybridization and polymerase chain reaction. Automated quantitative fluorescent immunohistochemistry was conducted to measure epithelial and stromal expression of carbonic anhydrase IX (CAIX) and glucose transporter 1 (GLUT1). Results: High stromal CAIX expression was associated with significantly reduced overall survival (p = 0.03) in patients with p16-negative tumors. Conclusions: This is the first study to use quantitative immunohistochemistry to examine endogenous markers of hypoxia stratified by tumor p16/HPV status. Assessment of CAIX expression in p16-negative HNSCC could identify patients with the least favorable prognosis and inform therapeutic strategies.
- OSTI ID:
- 21491717
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 1 Vol. 80; ISSN IOBPD3; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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ANOXIA
BIOLOGICAL MARKERS
BIOTECHNOLOGY
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CARBON-OXYGEN LYASES
CARBONIC ANHYDRASE
CARCINOMAS
CHEMOTHERAPY
DISEASES
ENZYMES
GENE AMPLIFICATION
GENETIC ENGINEERING
HEAD
HYDRO-LYASES
IN-SITU HYBRIDIZATION
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NEOPLASMS
NUCLEAR MEDICINE
NUCLEIC ACID HYBRIDIZATION
ORGANIC COMPOUNDS
POLYMERASE CHAIN REACTION
PROTEINS
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