Expression of cytochrome P450 3A4 and its clinical significance in human prostate cancer.
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.
Fujimura
Tetsuya
T
Department of Urology, University of Tokyo, Japan. jolly-poo@mub.biglobe.ne.jp
Takahashi
Satoru
S
Urano
Tomohiko
T
Kumagai
Jinpei
J
Murata
Taro
T
Takayama
Kenichi
K
Ogushi
Tetsuo
T
Horie-Inoue
Kuniko
K
Ouchi
Yasuyoshi
Y
Kitamura
Tadaichi
T
Muramatsu
Masami
M
Homma
Yukio
Y
Inoue
Satoshi
S
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
D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human