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.
Carnell
Dawn M
DM
Marie Curie Research Wing, Mount Vernon Hospital, Northwood, Middlesex, United Kingdom.
Smith
Rowena E
RE
Daley
Frances M
FM
Saunders
Michele I
MI
Bentzen
Søren M
SM
Hoskin
Peter J
PJ
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