Immunohistochemical evaluation of cytochrome P450 (CYP) and p53 in breast cancer.
In breast cancer, cytochrome P450 (CYP) metabolizes both endogenous substrates (i.e. estradiol) and exogenous substrates (i.e. anticancer drugs), which is associated not only with tumor development and progression but also with efficacy of cancer treatment. Therefore, we examined the expression of CYPs (CYP2A6, CYP1B1 and CYP3A) and p53 in specimens from 34 Japanese patients with breast cancer by immunohistochemistry. The expression of CYP3A was not detected in the 34 cases. CYP2A6 was detected only in one specimen (2.9%). Twenty-eight specimens (82.4%) showed positive signals for CYP1B1 expression. Eight of 34 (23.5%) were positive for p53 expression. Positive rate of CYP1B1 in stage I disease (100%) was statistically higher than that in stage II - IV disease (70.0%). Positive rate of p53 was 21.4% (6/28) in CYP1B1-positive cases and 33.3% (2/6) in CYP1B1-negative cases. There was no significant relationship between CYP1B1 expression and p53 expression. In conclusion, the expression of CYP3A in breast cancer may be less frequent in Japanese population although the expression of CYP3A has been reported in 20% of breast cancer in Caucasian, suggesting that the CYP3A expression in breast cancer may be dependent on ethnic groups. Since CYP3A is involved in the conversion of tamoxifen to its metabolites, the variation of the CYP3A expression in breast cancer tissues among ethnic groups might cause differences in the efficacy of tamoxifen.
Oyama
Tsunehiro
T
Second Department of Surgery, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan. oyama@med.uoeh-u.ac.jp <oyama@med.uoeh-u.ac.jp>
Morita
Masaru
M
Isse
Toyohi
T
Kagawa
Norio
N
Nakata
Shyouzi
S
So
Tetsuya
T
Mizukami
Makiko
M
Ichiki
Yoshinobu
Y
Ono
Kenji
K
Sugaya
Masakazu
M
Uramoto
Hidetaka
H
Yoshimatsu
Takashi
T
Hanagiri
Takeshi
T
Sugio
Kenji
K
Kawamoto
Toshihiro
T
Yasumoto
Kosei
K
D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology* / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D065637:Cytochrome P-450 CYP2A6; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism; D013629:Tamoxifen / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D004967:Estrogens; D016159:Tumor Suppressor Protein p53; D013629:Tamoxifen; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; C585710:CYP2A6 protein, human; D065633:Cytochrome P-450 CYP1B1; D065637:Cytochrome P-450 CYP2A6; D051544:Cytochrome P-450 CYP3A