Target validation of cytochrome P450CYP1B1 in prostate carcinoma with protein expression in associated hyperplastic and premalignant tissue

D M Carnell, R E Smith, F M Daley, P R Barber, P J Hoskin, G D Wilson, G I Murray, S A Everett

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Abstract

Purpose: 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 and Materials: 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. (C) 2004 Elsevier Inc.

Original languageEnglish
Pages (from-to)500-509
Number of pages10
JournalInternational Journal of Radiation Oncology, Biology, Physics
Volume58
DOIs
Publication statusPublished - 2004

Keywords

  • cytochrome P450CYP1B1
  • prostate carcinoma
  • bladder carcinoma
  • radiation
  • hyperplasia
  • PIN
  • spectral imaging microscopy
  • INTRAEPITHELIAL NEOPLASIA
  • CELL RADIOSENSITIZATION
  • GENE-EXPRESSION
  • CANCER-RESEARCH
  • NITRIC-OXIDE
  • CYP1B1
  • PREVALENCE
  • ACTIVATION
  • MECHANISM
  • PATTERNS

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