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Title: Hypoxia in relation to vasculature and proliferation in liver metastases in patients with colorectal cancer

Abstract

Purpose: To investigate hypoxia measured by pimonidazole binding, glucose transporter 1 (GLUT1) and carbonic anhydrase IX (CA-IX) expression, proliferation, and vascularity in liver metastases of colorectal cancer and to compare GLUT1 and CA-IX expression in corresponding primary tumors. Methods and Materials: Twenty-five patients with liver metastases of colorectal cancer, planned for metastasectomy, were included. The hypoxia marker pimonidazole and proliferation marker iododeoxyuridine were administered before surgery. After immunofluorescent staining of the frozen metastases, pimonidazole binding, vascularity, and proliferation were analyzed quantitatively. Thirteen paraffin-embedded primary tumors were stained immunohistochemically for GLUT1 and CA-IX expression, which was analyzed semiquantitatively in primary tumors and corresponding liver metastases. Results: In liver metastases, pimonidazole binding showed a pattern consistent with diffusion-limited hypoxia. The mean pimonidazole-positive fraction was 0.146; the mean distance from vessels to pimonidazole-positive areas was 80 {mu}m. When expressed, often co-localization was observed between pimonidazole binding and GLUT1 or CA-IX expression, but microregional areas of mismatch were also observed. No correlation between the level of pimonidazole binding and GLUT1 or CA-IX expression was observed. In some patients, a large fraction (up to 30%) of proliferating cells was present in pimonidazole-stained areas. Expression of CA-IX in primary tumors and metastases showed a significant correlation,more » which was absent for GLUT1 expression. Conclusions: Compared with other tumor types, liver metastases of colorectal cancer contain large amounts of hypoxic cells. The lack of correlation with pimonidazole binding brings into question the value of GLUT1 and CA-IX as endogenous markers of hypoxia.« less

Authors:
 [1];  [2];  [2];  [2];  [2];  [3];  [3];  [4];  [5];  [2]
  1. Department of Medical Oncology, Radboud University Nijmegen Medical Center, Nijmegen (Netherlands). E-mail: h.vanlaarhoven@onco.umcn.nl
  2. Department of Radiation Oncology, Radboud University Nijmegen Medical Center, Nijmegen (Netherlands)
  3. Department of Surgery, Radboud University Nijmegen Medical Center, Nijmegen (Netherlands)
  4. Department of Medical Oncology, Radboud University Nijmegen Medical Center, Nijmegen (Netherlands)
  5. Department of Radiology, Radboud University Nijmegen Medical Center, Nijmegen (Netherlands)
Publication Date:
OSTI Identifier:
20793307
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 64; Journal Issue: 2; Other Information: DOI: 10.1016/j.ijrobp.2005.07.982; PII: S0360-3016(05)02374-6; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANOXIA; CARBONIC ANHYDRASE; CARCINOMAS; GLUCOSE; IODODEOXYURIDINE; LIVER; METASTASES; PARAFFIN; PATIENTS; SURGERY

Citation Formats

Laarhoven, Hanneke W.M. van, Kaanders, Johannes, Lok, Jasper, Peeters, Wenny J.M., Rijken, Paul F.J.W., Wiering, Bastiaan, Ruers, Theo J.M., Punt, Cornelis J.A., Heerschap, Arend, and Kogel, Albert J. van der. Hypoxia in relation to vasculature and proliferation in liver metastases in patients with colorectal cancer. United States: N. p., 2006. Web. doi:10.1016/J.IJROBP.2005.0.
Laarhoven, Hanneke W.M. van, Kaanders, Johannes, Lok, Jasper, Peeters, Wenny J.M., Rijken, Paul F.J.W., Wiering, Bastiaan, Ruers, Theo J.M., Punt, Cornelis J.A., Heerschap, Arend, & Kogel, Albert J. van der. Hypoxia in relation to vasculature and proliferation in liver metastases in patients with colorectal cancer. United States. doi:10.1016/J.IJROBP.2005.0.
Laarhoven, Hanneke W.M. van, Kaanders, Johannes, Lok, Jasper, Peeters, Wenny J.M., Rijken, Paul F.J.W., Wiering, Bastiaan, Ruers, Theo J.M., Punt, Cornelis J.A., Heerschap, Arend, and Kogel, Albert J. van der. Wed . "Hypoxia in relation to vasculature and proliferation in liver metastases in patients with colorectal cancer". United States. doi:10.1016/J.IJROBP.2005.0.
@article{osti_20793307,
title = {Hypoxia in relation to vasculature and proliferation in liver metastases in patients with colorectal cancer},
author = {Laarhoven, Hanneke W.M. van and Kaanders, Johannes and Lok, Jasper and Peeters, Wenny J.M. and Rijken, Paul F.J.W. and Wiering, Bastiaan and Ruers, Theo J.M. and Punt, Cornelis J.A. and Heerschap, Arend and Kogel, Albert J. van der},
abstractNote = {Purpose: To investigate hypoxia measured by pimonidazole binding, glucose transporter 1 (GLUT1) and carbonic anhydrase IX (CA-IX) expression, proliferation, and vascularity in liver metastases of colorectal cancer and to compare GLUT1 and CA-IX expression in corresponding primary tumors. Methods and Materials: Twenty-five patients with liver metastases of colorectal cancer, planned for metastasectomy, were included. The hypoxia marker pimonidazole and proliferation marker iododeoxyuridine were administered before surgery. After immunofluorescent staining of the frozen metastases, pimonidazole binding, vascularity, and proliferation were analyzed quantitatively. Thirteen paraffin-embedded primary tumors were stained immunohistochemically for GLUT1 and CA-IX expression, which was analyzed semiquantitatively in primary tumors and corresponding liver metastases. Results: In liver metastases, pimonidazole binding showed a pattern consistent with diffusion-limited hypoxia. The mean pimonidazole-positive fraction was 0.146; the mean distance from vessels to pimonidazole-positive areas was 80 {mu}m. When expressed, often co-localization was observed between pimonidazole binding and GLUT1 or CA-IX expression, but microregional areas of mismatch were also observed. No correlation between the level of pimonidazole binding and GLUT1 or CA-IX expression was observed. In some patients, a large fraction (up to 30%) of proliferating cells was present in pimonidazole-stained areas. Expression of CA-IX in primary tumors and metastases showed a significant correlation, which was absent for GLUT1 expression. Conclusions: Compared with other tumor types, liver metastases of colorectal cancer contain large amounts of hypoxic cells. The lack of correlation with pimonidazole binding brings into question the value of GLUT1 and CA-IX as endogenous markers of hypoxia.},
doi = {10.1016/J.IJROBP.2005.0},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 64,
place = {United States},
year = {Wed Feb 01 00:00:00 EST 2006},
month = {Wed Feb 01 00:00:00 EST 2006}
}