Expression of xenobiotic and steroid hormone metabolizing enzymes in human breast carcinomas.
The potential to metabolize endogenous and exogenous substances may influence breast cancer development and tumor growth. Therefore, the authors investigated the protein expression of Glutathione S-transferase (GST) isoforms and cytochrome P450 (CYP) known to be involved in the metabolism of steroid hormones and endogenous as well as exogenous carcinogens in breast cancer tissue to obtain new information on their possible role in tumor progression. Expression of GST pi, mu, alpha and CYP1A1/2, 1A2, 3A4/5, 1B1, 2E1 was assessed by immunohistochemistry for primary breast carcinomas of 393 patients from the German GENICA breast cancer collection. The percentages of positive tumors were 50.1 and 44.5% for GST mu and CYP2E1, and ranged from 13 to 24.7% for CYP1A2, GST pi, CYP1A1/2, CYP3A4/5, CYP1B1. GST alpha was expressed in 1.8% of tumors. The authors observed the following associations between strong protein expression and histopathological characteristics: GST expression was associated with a better tumor differentiation (GST mu, p = 0.018) and with reduced lymph node metastasis (GST pi, p = 0.02). In addition, GST mu expression was associated with a positive estrogen receptor and progesterone receptor status (p < 0.001). CYP3A4/5 expression was associated with a positive nodal status (p = 0.018). Expression of CYP1B1 was associated with poor tumor differentiation (p = 0.049). Our results demonstrate that the majority of breast carcinomas expressed xenobiotic and drug metabolizing enzymes. They particularly suggest that GST mu and pi expression may indicate a better prognosis and that strong CYP3A4/5 and CYP1B1 expression may be key features of nonfavourable prognosis.
Haas
Susanne
S
Institute of Pathology, Medical Faculty of the University of Bonn, Sigmund Freud Street 25, D-53127 Bonn, Germany. Susanne.Haas@ukb.uni-bonn.de
Pierl
Christiane
C
Harth
Volker
V
Pesch
Beate
B
Rabstein
Sylvia
S
Brüning
Thomas
T
Ko
Yon
Y
Hamann
Ute
U
Justenhoven
Christina
C
Brauch
Hiltrud
H
Fischer
Hans-Peter
HP
D000368:Aged; D001943:Breast Neoplasms / Q000145:classification / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D013256:Steroids / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism*
D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase; D006728:Hormones; D018719:Erb-b2 Receptor Tyrosine Kinases; D013256:Steroids; D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases; D015262:Xenobiotics; C513496:MIB1 ligase, human