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Title: An immunohistochemical assessment of hypoxia in prostate carcinoma using pimonidazole: Implications for radioresistance

Abstract

Purpose: To investigate the presence of hypoxia in human prostate carcinoma by using pimonidazole immunohistochemical labeling in radical prostatectomy specimens. Methods and Materials: Forty-three patients (median age, 69 years; range, 49-83 years) with localized prostate adenocarcinoma received 0.5 gm/m{sup 2} i.v. pimonidazole 16-24 h before radical prostatectomy. Hypoxia was detected with a monoclonal antibody directed against pimonidazole and scored in formalin-fixed, paraffin-embedded sections. Median and maximal vessel counts were measured with CD34. Results: Thirty-seven patients completed the study. Pimonidazole binding was present in prostate carcinomas in 34 of 37 patients (92%) and in benign prostatic hyperplasia in 35 of 37 patients (95%). A positive correlation of 3+ pimonidazole binding with Gleason score was demonstrated (Spearman's rank, p = 0.044). Vascularity scores did not correlate with hypoxic status or clinical prognostic parameters. Conclusion: Prostate carcinoma and benign prostatic hyperplasia have significant areas of hypoxia; greater hypoxia scores are seen with more aggressive prostate cancer. It is postulated that a hypoxic microenvironment within the prostate might be responsible for the promotion of secondary genetic alterations and angiogenic stimulation, leading to malignant progression, a more aggressive cell phenotype, and greater radioresistance. Modification of radiation regimens to specifically target hypoxia might improve local tumormore » control.« less

Authors:
 [1];  [2];  [3];  [4];  [5];  [4]
  1. Marie Curie Research Wing, Mount Vernon Hospital, Northwood, Middlesex (United Kingdom). E-mail: peterhoskin@nhs.net
  2. Department of Histopathology, Mount Vernon Hospital, Northwood, Middlesex (United Kingdom)
  3. Gray Cancer Institute, Mount Vernon Hospital, Northwood, Middlesex (United Kingdom)
  4. Marie Curie Research Wing, Mount Vernon Hospital, Northwood, Middlesex (United Kingdom)
  5. Department of Human Oncology, University of Wisconsin, Madison, WI (United States)
Publication Date:
OSTI Identifier:
20793461
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 65; Journal Issue: 1; Other Information: DOI: 10.1016/j.ijrobp.2005.11.044; PII: S0360-3016(05)03078-6; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The 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; CARCINOMAS; FORMALDEHYDE; LABELLING; MONOCLONAL ANTIBODIES; PARAFFIN; PATIENTS; PHENOTYPE; PROSTATE; RADIOSENSITIVITY; STIMULATION

Citation Formats

Carnell, Dawn M., Smith, Rowena E., Daley, Frances, Saunders, Michele I., Bentzen, Soren M., and Hoskin, Peter J.. An immunohistochemical assessment of hypoxia in prostate carcinoma using pimonidazole: Implications for radioresistance. United States: N. p., 2006. Web. doi:10.1016/J.IJROBP.2005.1.
Carnell, Dawn M., Smith, Rowena E., Daley, Frances, Saunders, Michele I., Bentzen, Soren M., & Hoskin, Peter J.. An immunohistochemical assessment of hypoxia in prostate carcinoma using pimonidazole: Implications for radioresistance. United States. doi:10.1016/J.IJROBP.2005.1.
Carnell, Dawn M., Smith, Rowena E., Daley, Frances, Saunders, Michele I., Bentzen, Soren M., and Hoskin, Peter J.. Mon . "An immunohistochemical assessment of hypoxia in prostate carcinoma using pimonidazole: Implications for radioresistance". United States. doi:10.1016/J.IJROBP.2005.1.
@article{osti_20793461,
title = {An immunohistochemical assessment of hypoxia in prostate carcinoma using pimonidazole: Implications for radioresistance},
author = {Carnell, Dawn M. and Smith, Rowena E. and Daley, Frances and Saunders, Michele I. and Bentzen, Soren M. and Hoskin, Peter J.},
abstractNote = {Purpose: To investigate the presence of hypoxia in human prostate carcinoma by using pimonidazole immunohistochemical labeling in radical prostatectomy specimens. Methods and Materials: Forty-three patients (median age, 69 years; range, 49-83 years) with localized prostate adenocarcinoma received 0.5 gm/m{sup 2} i.v. pimonidazole 16-24 h before radical prostatectomy. Hypoxia was detected with a monoclonal antibody directed against pimonidazole and scored in formalin-fixed, paraffin-embedded sections. Median and maximal vessel counts were measured with CD34. Results: Thirty-seven patients completed the study. Pimonidazole binding was present in prostate carcinomas in 34 of 37 patients (92%) and in benign prostatic hyperplasia in 35 of 37 patients (95%). A positive correlation of 3+ pimonidazole binding with Gleason score was demonstrated (Spearman's rank, p = 0.044). Vascularity scores did not correlate with hypoxic status or clinical prognostic parameters. Conclusion: Prostate carcinoma and benign prostatic hyperplasia have significant areas of hypoxia; greater hypoxia scores are seen with more aggressive prostate cancer. It is postulated that a hypoxic microenvironment within the prostate might be responsible for the promotion of secondary genetic alterations and angiogenic stimulation, leading to malignant progression, a more aggressive cell phenotype, and greater radioresistance. Modification of radiation regimens to specifically target hypoxia might improve local tumor control.},
doi = {10.1016/J.IJROBP.2005.1},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 65,
place = {United States},
year = {Mon May 01 00:00:00 EDT 2006},
month = {Mon May 01 00:00:00 EDT 2006}
}