Immunohistochemical detection of changes in tumor hypoxia Journal Article


Authors: Russell, J.; Carlin, S.; Burke, S. A.; Wen, B.; Yang, K. M.; Ling, C. C.
Article Title: Immunohistochemical detection of changes in tumor hypoxia
Abstract: Purpose: Although hypoxia is a known prognostic factor, its effect will be modified by the rate of reoxygenation and the extent to which the cells are acutely hypoxic. We tested the ability of exogenous and endogenous markers to detect reoxygenation in a xenograft model. Our technique might be applicable to stored patient samples. Methods and Materials: The human colorectal carcinoma line, HT29, was grown in nude mice. Changes in tumor hypoxia were examined by injection of pimonidazole, followed 24 hours later by EF5. Cryosections were stained for these markers and for carbonic anhydrase IX (CAIX) and hypoxia-inducible factor 1α (HIF1α). Tumor hypoxia was artificially manipulated by carbogen exposure. Results: In unstressed tumors, all four markers showed very similar spatial distributions. After carbogen treatment, pimonidazole and EF5 could detect decreased hypoxia. HIF1α staining was also decreased relative to CAIX, although the effect was less pronounced than for EF5. Control tumors displayed small regions that had undergone spontaneous changes in tumor hypoxia, as judged by pimonidazole relative to EF5; most of these changes were reflected by CAIX and HIF1α. Conclusion: HIF1α can be compared with either CAIX or a previously administered nitroimidazole to provide an estimate of reoxygenation. © 2009 Elsevier Inc. All rights reserved.
Keywords: immunohistochemistry; protein expression; human cell; cancer patient; animals; mice; enzyme inhibition; oxygen; tumor markers, biological; oncology; tumor marker; risk factor; antigens, neoplasm; xenograft; nude mouse; mice, nude; tumors; prognostic factors; tumor cell; pimonidazole; cell hypoxia; radiation-sensitizing agents; hypoxia inducible factor 1alpha; cell strain ht29; ht29 cells; nitroimidazoles; hypoxia-inducible factor 1, alpha subunit; carbonic anhydrase ix; ef5; hypoxia inducible factor 1α; reoxygenation; carbogen; colorectal carcinomata; nitroimidazole; small regions; spatial distributions; tumor hypoxias; 2 (2 nitro 1h imidazol 1 yl) n (2,2,3,3,3 pentafluoropropyl)acetamide; carbonate dehydratase; tumor cell hypoxia; carbon dioxide; carbonic anhydrases; etanidazole; hydrocarbons, fluorinated
Journal Title: International Journal of Radiation Oncology, Biology, Physics
Volume: 73
Issue: 4
ISSN: 0360-3016
Publisher: Elsevier Inc.  
Date Published: 2009-03-15
Start Page: 1177
End Page: 1186
Language: English
DOI: 10.1016/j.ijrobp.2008.12.004
PUBMED: 19251089
PROVIDER: scopus
PMCID: PMC2680715
DOI/URL:
Notes: --- - "Cited By (since 1996): 5" - "Export Date: 30 November 2010" - "CODEN: IOBPD" - "Source: Scopus"
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Bixiu Wen
    23 Wen
  2. Kwang Mo Yang
    2 Yang
  3. James Russell
    41 Russell
  4. Sean Denis Carlin
    83 Carlin
  5. C Clifton Ling
    331 Ling
  6. Sean A Burke
    5 Burke