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mdr1 mRNA expression by RT-PCR in patients with primary breast cancer submitted to neoadjuvant therapy

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Abstract

mdr1 expression by reverse transcription and polymerase chain reaction(RT-PCR) has been compared to P-glycoprotein (Pgp) expression byimmunohistochemistry (IHC) and correlated with clinical response toneoadjuvant therapy. RNA has been recovered from glass slide smears offine-needle aspiration from 57 untreated primary breast cancers prior toneoadjuvant chemotherapy (33 cases), hormone therapy (23 cases), or both (1case). Furthermore, mdr1 mRNA has been analyzed in 6 cases after 2 months oftreatment. The neoadjuvant therapy consisted of 4 cycles of adriamycin andcyclophosphamide or tamoxifen. Of 57 tumor specimens, an interpretableresult was obtained in 52 cases, indicating the feasibility of the analysisby RT-PCR with very small tumor specimens. The presence of mdr1 mRNA hasbeen documented in 44/52 (84%) tumor samples with a spectrum ofexpression levels. The expression of mdr1 mRNA was compared withP-glycoprotein (Pgp) expression by IHC using JSB-1, 4E3, and C494 monoclonalantibodies in 48 of the 52 interpretable tumor samples. 12/48 (25%)expressed Pgp by IHC. All tumors expressing Pgp by IHC were also positive byRT-PCR. The results confirm the higher prevalence of mdr1 mRNA compared tothe protein expression. However, mdr1 mRNA expression was found to correlatesignificantly with resistance to neoadjuvant hormone therapy only while Pgpexpression detected by JSB-1 immunostaining only correlated withchemoresistance. The lack of convincing correlation with chemoresistancesuggests that mRNA and Pgp may not be directly or solely responsible forclinical response to drugs. Further studies should focus on theposttranslational modulation of P-glycoprotein and other mechanisms of drugresistance.

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Authors and Affiliations

  1. Centre de Recherche en Cancérologie, Centre Hospitalier, Universitaire de Québec, Pavillon Hôtel-Dieu de Québec, Université Laval, Canada

    Chang Shu Wang & Hélène Larue

  2. Department of Radiation Oncology, Centre Hospitalier Universitaire de Québec, Pavillon Hôtel-Dieu de Québec, Université Laval, Canada

    André Fortin

  3. Centre d'Oncologie, Hôpital St-Luc, Montréal, Canada

    Gilles Gariépy

  4. Department of Pathology, Centre Hospitalier Universitaire de Québec, Pavillon Hôtel-Dieu de Québec, Université Laval, Canada

    Bernard Têtu

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  1. Chang Shu Wang
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Wang, C.S., Larue, H., Fortin, A. et al. mdr1 mRNA expression by RT-PCR in patients with primary breast cancer submitted to neoadjuvant therapy. Breast Cancer Res Treat 45, 63–74 (1997). https://doi.org/10.1023/A:1005824704740

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