Target validation of cytochrome P450 CYP1B1 in prostate carcinoma with protein expression in associated hyperplastic and premalignant tissue.
OBJECTIVE
To investigate the localization and distribution of cytochrome P450 CYP1B1 protein expression in patients diagnosed with prostate carcinoma compared to those with bladder carcinoma. To validate CYP1B1 as a molecular target for the development of selective cancer therapeutics for use in combination with radiation.


METHODS
Prostatectomy specimens (n = 33) of moderate Gleason grade (3 + 3 and 3 + 4) were analyzed immunohistochemically for CYP1B1 protein expression using a specific monoclonal antibody for the enzyme. The intensity of CYP1B1 staining was assessed both semiquantitatively using visual scoring and quantitatively by spectral imaging microscopy using reference spectra and compared with bladder carcinoma (n = 22).


RESULTS
CYP1B1 protein expression was present in 75% of prostate carcinomas (n = 27) compared to 100% of bladder carcinomas (n = 22). In both cases, CYP1B1 protein expression was heterogeneous and localized in the cytoplasm of the tumor cells but absent from the surrounding stromal tissue. CYP1B1 was also detected in premalignant prostatic intraepithelial neoplasia (n = 2, 100%), as well as noncancerous tissues, including benign prostatic hyperplasia (n = 27, 82%), metaplastic prostatic urothelium (n = 8, 100%), and hyperplastic prostatic urothelium (n = 14, 100%). Higher CYP1B1 protein expression in bladder vs. prostate carcinoma was confirmed by their corresponding average normalized absorbances (+/- standard deviation), measured as 1.40 +/- 0.44 and 0.55 +/- 0.09, respectively. Overall CYP1B1 staining intensity in prostate carcinoma was similar to that in prostatic intraepithelial neoplasia, benign prostatic hyperplasia, and hyper-/metaplastic urothelial tissue. No CYP1B1 was detected in normal prostate tissue.


CONCLUSIONS
CYP1B1 is overexpressed in prostate carcinoma at a high frequency and is also detectable in the associated premalignant and hyperplastic tissue, implicating a possible link with malignant progression and CYP1B1 as a suitable target for therapy. Spectral imaging microscopy has highlighted differences in CYP1B1 protein expression between different cancers.
Carnell
Dawn M
DM
Marie Curie Research Wing, Gray Cancer Institute, Mount Vernon Hospital, Northwood, Middlesex HA6 2JR, United Kingdom
Smith
Rowena E
RE
Daley
Frances M
FM
Barber
Paul R
PR
Hoskin
Peter J
PJ
Wilson
George D
GD
Murray
Graeme I
GI
Everett
Steven A
SA
D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D065633:Cytochrome P-450 CYP1B1; D003593:Cytoplasm / Q000201:enzymology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011230:Precancerous Conditions / Q000201:enzymology*; D011446:Prospective Studies; D019048:Prostatic Intraepithelial Neoplasia / Q000201:enzymology; D011471:Prostatic Neoplasms / Q000201:enzymology*; D001749:Urinary Bladder Neoplasms / Q000201:enzymology; D019459:Urothelium / Q000201:enzymology
D009363:Neoplasm Proteins; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1