Hypoxia in human colorectal adenocarcinoma: Comparison between extrinsic and potential intrinsic hypoxia markers
- Department of Radiation Oncology, University Hospital Gasthuisberg, Leuven (Belgium)
- Department of Applied Mathematics, Royal Military Academy, Brussels (Belgium)
- Department of Pathology, University Hospital Gasthuisberg, Leuven (Belgium)
- Department of Abdominal Surgery, University Hospital Gasthuisberg, Leuven (Belgium)
- Department of Radiation Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (United States)
- Division of Experimental Therapy, Netherlands Cancer Institute, Amsterdam (Netherlands)
Purpose: To detect and quantify hypoxia in colorectal adenocarcinomas by use of pimonidazole and iododeoxyuridine (IdUrd) as extrinsic markers and carbonic anhydrase IX (CA IX), microvessel density (MVD), epidermal growth-factor receptor (EGFR), and vascular endothelial growth factor (VEGF) as intrinsic markers of hypoxia. Methods and Material: Twenty patients with an adenocarcinoma of the left colon and rectum treated by primary surgery were injected with pimonidazole and IdUrd. Serial sections of tumor biopsies were single stained for VEGF, EGFR, Ki67, and double stained for blood vessels in combination with either pimonidazole, IdUrd, or CA IX. Percentage of expression was scored as well as colocalization of pimonidazole with CA IX. Results: The median percentage of hypoxia, as judged by pimonidazole staining, was 16.7% (range, 0-52.4%). The expression of pimonidazole correlated inversely with the total MVD and endothelial cord MVD (R = -0.55, p = 0.01; R = -0.47, p = 0.04). Good colocalization was found between pimonidazole and CA IX in only 30% of tumors, with no correlation overall between pimonidazole and CA IX, VEGF, or EGFR or between the different intrinsic markers. Cells around some vessels (0.08-11%) were negative for IdUrd but positive for Ki 67, which indicated their lack of perfusion at the time of injection. Conclusion: Chronic and acute hypoxic regions are present in colorectal tumors, as shown by pimonidazole and IdUrd staining. Only in a minority of tumors did an association exist between the areas stained by pimonidazole and those positive for CA IX. Pimonidazole also did not correlate with expression of other putative intrinsic hypoxia markers (VEGF, EGFR)
- OSTI ID:
- 20793481
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 65, Issue 1; Other Information: DOI: 10.1016/j.ijrobp.2006.01.007; PII: S0360-3016(06)00094-0; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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