An immunohistochemical assessment of hypoxia in prostate carcinoma using pimonidazole: implications for radioresistance.
OBJECTIVE
To investigate the presence of hypoxia in human prostate carcinoma by using pimonidazole immunohistochemical labeling in radical prostatectomy specimens.


METHODS
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.


CONCLUSIONS
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.
Marie Curie Research Wing, Mount Vernon Hospital, Northwood, Middlesex, United Kingdom.
Dawn M
DM
Carnell
Rowena E
RE
Smith
Frances M
FM
Daley
Michele I
MI
Saunders
Søren M
SM
Bentzen
Peter J
PJ
Hoskin
D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology; D015687:Cell Hypoxia / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009593:Nitroimidazoles / Q000276:immunology / Q000493:pharmacokinetics*; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics*
D000911:Antibodies, Monoclonal; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C033815:pimonidazole