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.
OBJECTIVE
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
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.


CONCLUSIONS
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.
Bache
Matthias
M
Department of Radiotherapy, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
Reddemann
Rolf
R
Said
Harun M
HM
Holzhausen
Hans-Jürgen
HJ
Taubert
Helge
H
Becker
Axel
A
Kuhnt
Thomas
T
Hänsgen
Gabriele
G
Dunst
Jürgen
J
Vordermark
Dirk
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000032:analysis / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000032:analysis / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000032:analysis / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D011379:Prognosis; D012044:Regression Analysis; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D006454:Hemoglobins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D053495:Osteopontin; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D010100:Oxygen