skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Expression of EGFR Under Tumor Hypoxia: Identification of a Subpopulation of Tumor Cells Responsible for Aggressiveness and Treatment Resistance

Abstract

Purpose: Overexpression of epidermal growth factor receptor (EGFR) and tumor hypoxia have been shown to correlate with worse outcome in several types of cancer including head-and-neck squamous cell carcinoma. Little is known about the combination and possible interactions between the two phenomena. Methods and Materials: In this study, 45 cases of histologically confirmed squamous cell carcinomas of the head and neck were analyzed. All patients received intravenous infusions of the exogenous hypoxia marker pimonidazole prior to biopsy. Presence of EGFR, pimonidazole binding, and colocalization between EGFR and tumor hypoxia were examined using immunohistochemistry. Results: Of all biopsies examined, respectively, 91% and 60% demonstrated EGFR- and pimonidazole-positive areas. A weak but significant association was found between the hypoxic fractions of pimonidazole (HFpimo) and EGFR fractions (F-EGFR) and between F-EGFR and relative vascular area. Various degrees of colocalization between hypoxia and EGFR were found, increasing with distance from the vasculature. A high fraction of EGFR was correlated with better disease-free and metastasis-free survival, whereas a high degree of colocalization correlated with poor outcome. Conclusions: Colocalization of hypoxia and EGFR was demonstrated in head-and-neck squamous cell carcinomas, predominantly at longer distances from vessels. A large amount of colocalization was associated with poor outcome,more » which points to a survival advantage of hypoxic cells that are also able to express EGFR. This subpopulation of tumor cells might be indicative of tumor aggressiveness and be partly responsible for treatment resistance.« less

Authors:
 [1]; ;  [2]; ; ; ;  [1]
  1. Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)
  2. Department of Otorhinolaryngology/Head-Neck Surgery, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)
Publication Date:
OSTI Identifier:
22149602
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics
Additional Journal Information:
Journal Volume: 84; Journal Issue: 3; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0360-3016
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANOXIA; BIOPSY; CARCINOMAS; GROWTH FACTORS; HEAD; INTERACTIONS; METASTASES; NECK; PATIENTS; RECEPTORS; TUMOR CELLS

Citation Formats

Hoogsteen, Ilse J., E-mail: i.hoogsteen@rther.umcn.nl, Marres, Henri A.M., Hoogen, Franciscus J.A. van den, Rijken, Paul F.J.W., Lok, Jasper, Bussink, Johan, and Kaanders, Johannes H.A.M. Expression of EGFR Under Tumor Hypoxia: Identification of a Subpopulation of Tumor Cells Responsible for Aggressiveness and Treatment Resistance. United States: N. p., 2012. Web. doi:10.1016/J.IJROBP.2012.01.002.
Hoogsteen, Ilse J., E-mail: i.hoogsteen@rther.umcn.nl, Marres, Henri A.M., Hoogen, Franciscus J.A. van den, Rijken, Paul F.J.W., Lok, Jasper, Bussink, Johan, & Kaanders, Johannes H.A.M. Expression of EGFR Under Tumor Hypoxia: Identification of a Subpopulation of Tumor Cells Responsible for Aggressiveness and Treatment Resistance. United States. doi:10.1016/J.IJROBP.2012.01.002.
Hoogsteen, Ilse J., E-mail: i.hoogsteen@rther.umcn.nl, Marres, Henri A.M., Hoogen, Franciscus J.A. van den, Rijken, Paul F.J.W., Lok, Jasper, Bussink, Johan, and Kaanders, Johannes H.A.M. Thu . "Expression of EGFR Under Tumor Hypoxia: Identification of a Subpopulation of Tumor Cells Responsible for Aggressiveness and Treatment Resistance". United States. doi:10.1016/J.IJROBP.2012.01.002.
@article{osti_22149602,
title = {Expression of EGFR Under Tumor Hypoxia: Identification of a Subpopulation of Tumor Cells Responsible for Aggressiveness and Treatment Resistance},
author = {Hoogsteen, Ilse J., E-mail: i.hoogsteen@rther.umcn.nl and Marres, Henri A.M. and Hoogen, Franciscus J.A. van den and Rijken, Paul F.J.W. and Lok, Jasper and Bussink, Johan and Kaanders, Johannes H.A.M.},
abstractNote = {Purpose: Overexpression of epidermal growth factor receptor (EGFR) and tumor hypoxia have been shown to correlate with worse outcome in several types of cancer including head-and-neck squamous cell carcinoma. Little is known about the combination and possible interactions between the two phenomena. Methods and Materials: In this study, 45 cases of histologically confirmed squamous cell carcinomas of the head and neck were analyzed. All patients received intravenous infusions of the exogenous hypoxia marker pimonidazole prior to biopsy. Presence of EGFR, pimonidazole binding, and colocalization between EGFR and tumor hypoxia were examined using immunohistochemistry. Results: Of all biopsies examined, respectively, 91% and 60% demonstrated EGFR- and pimonidazole-positive areas. A weak but significant association was found between the hypoxic fractions of pimonidazole (HFpimo) and EGFR fractions (F-EGFR) and between F-EGFR and relative vascular area. Various degrees of colocalization between hypoxia and EGFR were found, increasing with distance from the vasculature. A high fraction of EGFR was correlated with better disease-free and metastasis-free survival, whereas a high degree of colocalization correlated with poor outcome. Conclusions: Colocalization of hypoxia and EGFR was demonstrated in head-and-neck squamous cell carcinomas, predominantly at longer distances from vessels. A large amount of colocalization was associated with poor outcome, which points to a survival advantage of hypoxic cells that are also able to express EGFR. This subpopulation of tumor cells might be indicative of tumor aggressiveness and be partly responsible for treatment resistance.},
doi = {10.1016/J.IJROBP.2012.01.002},
journal = {International Journal of Radiation Oncology, Biology and Physics},
issn = {0360-3016},
number = 3,
volume = 84,
place = {United States},
year = {2012},
month = {11}
}