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Int J Radiat Oncol Biol Phys. 2006 May 1;65(1):91-9. Epub 2006 Mar 24.

An immunohistochemical assessment of hypoxia in prostate carcinoma using pimonidazole: implications for radioresistance.

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1
Marie Curie Research Wing, Mount Vernon Hospital, Northwood, Middlesex, United Kingdom.

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/m2 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.

PMID:
16563659
DOI:
10.1016/j.ijrobp.2005.11.044
[Indexed for MEDLINE]

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