title: Expression of cytochrome P450 3A4 and its clinical significance in human prostate cancer.
abstract: OBJECTIVE
  To evaluate CYP3A4 expression in human prostrate cancer (PCa) tissues. Enzymes of the cytochrome P450 (CYP) family are key inactivators of testosterone in the liver and prostate. We previously reported that CYP2B6 is a growth-inhibitory and prognostic factor in human PCa; however, the status of CYP3A4 in PCa remains unclear.
  
  
  METHODS
  We used immunohistochemistry to analyze CYP3A4 expression in 107 human PCa specimens obtained by radical prostatectomy. Stained slides were evaluated for the proportion and staining intensity of positively stained cells. Total immunoreactivity scores (0-8) were obtained as the sum of the proportion and intensity scores. In addition, we estimated the relationship between CYP3A4 status and clinicopathologic features.
  
  
  RESULTS
  CYP3A4 immunoreactivity was identified in the cytoplasm of prostate cells. The CYP3A4 immunoreactive PCa score (3.6+/-2.6) was significantly lower than that of benign epithelium (4.5+/-2.1; P < .0001). In addition, CYP3A4 immunoreactivity correlated inversely with the Gleason score (P < .0001). Decreased CYP3A4 immunoreactivity was significantly related to a poor prognosis in human PCa (P = .0175).
  
  
  CONCLUSIONS
  We demonstrated differential CYP3A4 expression in prostatic tissues, indicating that decreased CYP3A4 expression may contribute to the development of PCa.
authors.affiliation: Department of Urology, University of Tokyo, Japan. jolly-poo@mub.biglobe.ne.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fujimura
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Urano
authors.forename: Jinpei
authors.initials: J
authors.lastname: Kumagai
authors.forename: Taro
authors.initials: T
authors.lastname: Murata
authors.forename: Kenichi
authors.initials: K
authors.lastname: Takayama
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ogushi
authors.forename: Kuniko
authors.initials: K
authors.lastname: Horie-Inoue
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Ouchi
authors.forename: Tadaichi
authors.initials: T
authors.lastname: Kitamura
authors.forename: Masami
authors.initials: M
authors.lastname: Muramatsu
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
mesh_terms: D000368:Aged; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D003593:Cytoplasm / Q000201:enzymology; D004848:Epithelium / Q000201:enzymology; D022781:Hepatocytes / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000201:enzymology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011467:Prostate / Q000201:enzymology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology
chemical_list: D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human