TY - JOUR
T1 - Immunohistochemical detection of HIF-1α and CAIX in advanced head-and-neck cancer: Prognostic role and correlation with tumor markers and tumor oxygenation parameters
AU - Kappler, Matthias
AU - Taubert, Helge
AU - Holzhausen, Hans Jürgen
AU - Reddemann, Rolf
AU - Rot, Swetlana
AU - Becker, Axel
AU - Kuhnt, Thomas
AU - Dellas, Kathrin
AU - Dunst, Jürgen
AU - Vordermark, Dirk
AU - Hänsgen, Gabriele
AU - Bache, Matthias
N1 - Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2008/8
Y1 - 2008/8
N2 - Background: Tumor hypoxia has an impact on the outcome of cancer patients treated with radiotherapy. The validity of endogenous markers such as hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase isozyme IX (CAIX) to detect therapeutically relevant levels of hypoxia within tumors is controversially discussed. Furthermore, the association of these hypoxia markers with tumor markers or tumor oxygenation parameters is of importance for understanding the relationship between the different factors. Patients and Methods: Tumor tissue sections of 34 patients with advanced head-and-neck cancer treated with radio(chemo)therapy were assessed by immunohistochemistry for the expression of HIF-1α and CAIX. The relationships of both markers with tumor oxygenation parameters, molecular factors like P53, OPN, VEGF, VHL, survivin, and Ki67 levels, and clinical parameters were studied. Results: Bivariate analysis showed a significant correlation of HIF-1α expression with high P53 and high OPN expression, high serum VEGF levels, and low VHL and low Ki67 expression. The CAIX expression was inversely correlated with pH value and directly correlated with T-stage. However, no correlation was found between HIF-1α and CAIX expression. Neither in a univariate Cox proportional hazard regression nor in a Kaplan-Meier analysis did expression of HIF-1α or CAIX have a significant impact on clinical outcome. However, in a Kaplan-Meier analysis, the combination of both factors showed that patients with intratumoral overexpression of either HIF-1α or CAIX or both markers died on average 2 years earlier than patients whose tumors had low expression of both factors (p < 0.05). Conclusion: Expression of HIF-1α and CAIX was correlated with different tumor parameters. Only combined HIF-1α and CAIX expression was significantly predictive of patients' overall survival.
AB - Background: Tumor hypoxia has an impact on the outcome of cancer patients treated with radiotherapy. The validity of endogenous markers such as hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase isozyme IX (CAIX) to detect therapeutically relevant levels of hypoxia within tumors is controversially discussed. Furthermore, the association of these hypoxia markers with tumor markers or tumor oxygenation parameters is of importance for understanding the relationship between the different factors. Patients and Methods: Tumor tissue sections of 34 patients with advanced head-and-neck cancer treated with radio(chemo)therapy were assessed by immunohistochemistry for the expression of HIF-1α and CAIX. The relationships of both markers with tumor oxygenation parameters, molecular factors like P53, OPN, VEGF, VHL, survivin, and Ki67 levels, and clinical parameters were studied. Results: Bivariate analysis showed a significant correlation of HIF-1α expression with high P53 and high OPN expression, high serum VEGF levels, and low VHL and low Ki67 expression. The CAIX expression was inversely correlated with pH value and directly correlated with T-stage. However, no correlation was found between HIF-1α and CAIX expression. Neither in a univariate Cox proportional hazard regression nor in a Kaplan-Meier analysis did expression of HIF-1α or CAIX have a significant impact on clinical outcome. However, in a Kaplan-Meier analysis, the combination of both factors showed that patients with intratumoral overexpression of either HIF-1α or CAIX or both markers died on average 2 years earlier than patients whose tumors had low expression of both factors (p < 0.05). Conclusion: Expression of HIF-1α and CAIX was correlated with different tumor parameters. Only combined HIF-1α and CAIX expression was significantly predictive of patients' overall survival.
UR - http://www.scopus.com/inward/record.url?scp=56149101369&partnerID=8YFLogxK
U2 - 10.1007/s00066-008-1813-7
DO - 10.1007/s00066-008-1813-7
M3 - Journal articles
C2 - 18956515
AN - SCOPUS:56149101369
SN - 0179-7158
VL - 184
SP - 393
EP - 399
JO - Strahlentherapie und Onkologie
JF - Strahlentherapie und Onkologie
IS - 8
ER -