Immunohistochemical detection of osteopontin in advanced head-and-neck cancer: prognostic role and correlation with oxygen electrode measurements, hypoxia-inducible-factor-1alpha-related markers, and hemoglobin levels.

Abstract

PURPOSE:

The tumor-associated glycoprotein osteopontin (OPN) is discussed as a plasma marker of tumor hypoxia. However, the association of immunohistochemical OPN expression in tumor sections with tumor oxygenation parameters (HF5, median pO(2)), the hypoxia-related markers hypoxia-inducible factor-1alpha (HIF-1alpha) and carbonic anhydrase IX (CAIX), or hemoglobin and systemic vascular endothelial growth factor (VEGF) levels has not been investigated.

METHODS AND MATERIALS:

Tumor tissue sections of 34 patients with advanced head-and-neck cancer treated with radiotherapy were assessed by immunochemistry for the expression of OPN, HIF-1alpha, and CA IX. Relationship of OPN expression with tumor oxygenation parameters (HF5, median pO(2)), HIF-1alpha and CA IX expression, hemoglobin and serum VEGF level, and clinical parameters was studied.

RESULTS:

Bivariate analysis showed a significant correlation of positive OPN staining with low hemoglobin level (p = 0.02), high HIF-1alpha expression (p = 0.02), and high serum vascular endothelial growth factor level (p = 0.02) for advanced head-and-neck cancer. Furthermore, considering the 31 Stage IV patients, the median pO(2) correlated significantly with the OPN expression (p = 0.02). OPN expression alone had only a small impact on prognosis. However, in a univariate Cox proportional hazard regression model, the expression of either OPN or HIF-1alpha or CA IX was associated with a 4.1-fold increased risk of death (p = 0.02) compared with negativity of all three markers.

CONCLUSION:

Osteopontin expression detected immunohistochemically is associated with oxygenation parameters in advanced head-and-neck cancer. When the results of OPN, HIF-1alpha, and CA IX immunohistochemistry are combined into a hypoxic profile, a strong and statistically significant impact on overall survival is found.

• Authors: Matthias Bache, Rolf Reddemann, Harun M Said, Hans-Jürgen Holzhausen, Helge Taubert, Axel Becker, Thomas Kuhnt, Gabriele Hänsgen, Jürgen Dunst, Dirk Vordermark
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 66 Issue 5 Pg. 1481-7 (Dec 01 2006) ISSN: 0360-3016 [Print] United States
• PMID: 17056190 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Biomarkers, Tumor
• Hemoglobins
• Hypoxia-Inducible Factor 1, alpha Subunit
• Vascular Endothelial Growth Factor A
• Osteopontin
• CA9 protein, human
• Carbonic Anhydrase IX
• Carbonic Anhydrases
• Oxygen

Topics

• Adult
• Aged
• Aged, 80 and over
• Antigens, Neoplasm (analysis, metabolism)
• Biomarkers, Tumor (analysis, metabolism)
• Carbonic Anhydrase IX
• Carbonic Anhydrases (analysis, metabolism)
• Cell Hypoxia (physiology)
• Female
• Follow-Up Studies
• Head and Neck Neoplasms (metabolism, mortality, pathology, radiotherapy)
• Hemoglobins (analysis)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (analysis, metabolism)
• Immunohistochemistry
• Male
• Middle Aged
• Osteopontin (analysis, metabolism)
• Oxygen (metabolism)
• Partial Pressure
• Prognosis
• Regression Analysis
• Survival Analysis
• Vascular Endothelial Growth Factor A (blood)