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Determining MDR1 / P‐glycoprotein expression in breast cancer
Author(s) -
Faneyte Ian F.,
Kristel Petra M.P.,
van de Vijver Marc J.
Publication year - 2001
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 - 10.1002/1097-0215(20010701)93:1<114::aid-ijc1309>3.0.co;2-j
Subject(s) - immunohistochemistry , p glycoprotein , breast cancer , chemotherapy , biology , cancer , pathology , multiple drug resistance , microbiology and biotechnology , cancer research , medicine , drug resistance
The mechanism of chemotherapy resistance in breast cancer is unresolved. MDR1 /P‐glycoprotein (P‐Gp) over‐expression confers multidrug resistance in vitro and might play a role in clinical breast cancer. Studies using clinical samples have yielded conflicting results. MDR1 /P‐Gp mRNA expression was determined relative to the expression in normal human liver using TaqMan real‐time RT‐PCR (corrected for expression of the housekeeping gene PBGD ). Immunohistochemistry (IHC) was performed with monoclonal antibodies against P‐Gp (JSB1, C219). The positive control was SW1573/2R160, the intermediate control SW1573 and the negative control GLC4/ADR. We assayed 9 breast‐cancer cell lines by RT‐PCR and IHC, 52 carcinoma samples by RT‐PCR and 168 samples by IHC. SW1573/2R160 contained high levels of MDR1 /P‐Gp mRNA (1.0, equal to liver) and showed strong membranous staining. Expression of MDR1 /P‐Gp mRNA in SW1573 (0.05) and GLC4/ADR (3.2 × 10 –5 ) was not detectable by IHC. Very low levels of MDR1 /P‐Gp mRNA were measured in breast‐cancer cell lines (mean 3.1 × 10 –4 , range 1 to 12 × 10 –4 ), but P‐Gp was not detected by IHC. In 25 specimens from chemotherapy‐naive patients, MDR1 /P‐Gp mRNA levels varied from 1 to 11 × 10 –2 (mean 3.9 × 10 –2 ). In sections of 80 chemotherapy‐naive tumors, no membrane‐bound staining was observed in the tumor cells. Tumors of 27 anthracycline‐treated patients had comparable MDR1 /P‐Gp mRNA expression levels (mean 5.4 × 10 –2 ). P‐Gp was undetectable in 88 tumor samples of patients who had received anthracycline‐based chemotherapy. In breast cancer, MDR1 /P‐Gp mRNA is low or absent and P‐Gp levels in cancer cells are too low to detect by IHC. Chemotherapy exposure does not result in detectable MDR1 /P‐Gp over‐expression. © 2001 Wiley‐Liss, Inc.