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Expression of xenobiotic and steroid hormone metabolizing enzymes in human breast carcinomas
Author(s) -
Haas Susanne,
Pierl Christiane,
Harth Volker,
Pesch Beate,
Rabstein Sylvia,
Brüning Thomas,
Ko Yon,
Hamann Ute,
Justenhoven Christina,
Brauch Hiltrud,
Fischer HansPeter
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21915
Subject(s) - breast cancer , cyp1b1 , biology , immunohistochemistry , medicine , cytochrome p450 , endocrinology , cyp1a2 , estrogen receptor , breast carcinoma , cancer , cyp3a4 , cancer research , immunology , metabolism
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. © 2006 Wiley‐Liss, Inc.