Abstract
The long-term prognostic value of tumoural MDR1 and MRP, along with p53 and other classical parameters, was analysed on 85 node-positive breast cancer patients receiving anthracycline-based adjuvant therapy. All patients underwent tumour resection plus irradiation and adjuvant chemotherapy (the majority receiving fluorouracil–epirubicin–cyclophosphamide). Median follow-up for the 54 alive patients was 7.8 years. Mean age was 53.7 years (range 28–79) and 54 patients were post-menopausal. MDR1 and MRP expression were quantified according to an original reverse transcription polymerase chain reaction multiplex assay with colourimetric enzyme-linked immunosorbent assay detection(β2-microglobulin as control). P53 protein was analysed using an immunoluminometric assay (Sangtec). MDR1 expression varied within an 11-fold range (mean 94, median 83), MRP within a 45-fold range (mean 315, median 242) and p53 protein from the limit of detection (0.002 ng mg–1) up to 35.71 ng mg–1(mean 1.18, median 0.13 ng mg–1). P53 protein was significantly higher in oestrogen receptor (ER)-negative than in ER-positive tumours (P = 0.039). The higher the p53, the lower the MDR1 expression (P = 0.015, r = –0.27). P53 was not linked to progesterone receptor (PR) status, S phase fraction, or MRP. Significantly greater MDR1 expression was observed in grade I tumours (P = 0.029). No relationship was observed between MDR1 and MRP. Neither MDR1 nor MRP was linked to ER or PR status. Unlike MDR1, MRP was correlated with the S phase: the greater the MRP, the lower the S phase (P = 0.006, r = –0.42). Univariate Cox analyses revealed that MDR1, MRP, p53 and S phase had no significant influence on progression-free or specific survival. A tendency suggested that the greater the p53, the shorter the progression-free survival (P = 0.076 as continuous and 0.069 as dichotomous). © 2000 Cancer Research Campaign
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Abbaszadegan MR, Futscher BW, Klimecki WT, List A and Dalton WS (1994) Analysis of multidrug resistance-associated protein (MRP) messenger RNA in normal and malignant hematopoietic cells. Cancer Res 54: 4676–4679
Allred DC, Clark GM, Elledge R, Fuqua SAW, Brown RW, Chamness GC, Osborne CK and McGuire WL (1993) Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. J Natl Cancer Inst 85: 200–206
Barrand MA, Heppell-Parton AC, Wright KA, Rabbits PH and Twentyman PR (1994) A 190-kilodalton protein overexpressed in non-p-glycoprotein-containing multidrug resistant cells and its relationship to the MRP gene. J Natl Cancer Inst 86: 110–117
Beck WT, Grogan TM and Willman C (1996) Methods to detect P-glycoprotein-associated multidrug resistance in patients' tumors: consensus recommendations. Cancer Res 56: 3010–3020
Beck J, Bohnet B, Brügger D, Bader P, Dietl J, Scheper RJ, Kandolf R, Liu C, Niethammer D and Gekeler V (1998) Multiple gene expression analysis reveals distinct differences between G2and G3stage breast cancers and correlations of PKCnwith MDR1, MRP and LRP gene expression. Br J Cancer 77: 87–91
Bloom HJ and Richardson WW (1957) Histological grading and prognosis in breast cancer. Br J Cancer 11: 359–377
Castillo L, Milano G, Santini J, Demard F and Pierrefite V (1997) Analysis of retinoic acid receptor β expression in normal and malignant laryngeal mucosa by a sensitive and routine applicable reverse transcription-polymerase chain reaction enzyme-linked immunosorbent assay method. Clin Cancer Res 3: 2137–2142
Chin KV, Ueda K, Pastan I and Gottesman MM (1992) Modulation of activity of the promotor of the human MDR1 gene by ras and p53. Science 255: 459–462
Chomczynski P and Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Annal Biochem 162: 156–159
Dexter DW, Reddy RK, Geles KG, Bansal S, Myint MA, Rogakto A, Leighton JC and Goldstein LJ (1998) Quantitative reverse transcriptase-polymerase chain reaction measured expression of MDR1 and MRP in primary breast carcinoma. Clin Cancer Res 4: 1533–1542
Early Breast Cancer Trialists’ Collaborative Group (1992) Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy: 133 randomised trials involving 31 000 recurrences and 24 000 deaths among 75 000 women. Lancet 339: 71–85
Early Breast Cancer Trialists' Collaborative Group (1998) Polychemotherapy for early breast cancer: an overview of the randomized trials. Lancet 352: 930–942
Filipits M, Suchomel RW, Dekan G, Haider K, Valdimarsson G, Depisch D and Pirker R (1996) MRP and MDR1gene expression in primary breast carcinoma. Clin Cancer Res 2: 1231–1237
Gasparini G, Pozza F and Harris AL (1993) Evaluating the potential usefulness of new prognostic and predictive indicators in node-negative breast cancer patients. J Natl Cancer Inst 85: 1206–1219
Iacopetta B, Grieu F, Powell B, Soong R, McCaul K and Seshadri R (1998) Analysis of p53 gene mutation by polymerase chain reaction-single-strand conformation polymorphism provides independent prognostic information in node-negative breast cancer. Clin Cancer Res 4: 1597–1602
Lautier D, Canitrot Y, Deeley RG and Cole SPC (1996) Multidrug resistance mediated by the multidrug resistance protein (MRP) gene. Biochem Pharmacol 52: 967–977
Levesque MA, Yu H, Clark GM and Diamandis EP (1998) Enzyme-linked immunoabsorbent assay-detected p53 protein accumulation: a prognostic factor in a large breast cancer cohort. J Clin Oncol 16: 2641–2650
Linn SC, Giaccone G, Van Diest PJ, Blokhuis WMD, Van der Valk P, Van Kalken CK, Kuiper CM, Pinedo HM and Baak JPA (1995) Prognostic relevance of P-glycoprotein expression in breast cancer. Annal Oncol 6: 679–685
Lowe SW, Ruley HE, Jacks T and Housman DE (1993) P53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74: 957–967
Lowe SW, Bodis S, McClatchey A, Remington L, Ruley HE, Fisher DE, Housman DE and Jacks T (1994) P53 status and the efficacy of cancer therapy in vivo. Science 266: 807–810
Muss HB, Thor AD, Berry DA, Kute T, Liu ET, Koerner F, Cirrincione CT, Budman DR, Wood WC, Barcos M and Henderson IC (1994) C-erb B-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med 330: 1260–1266
Namer M, Ramaioli A, Fontana X, Etienne MC, Hery M, Jourlait A, Milano G, Frenay M, François E and Lapalus F (1991) Prognostic value of total cathepsin D in breast tumors. A possible role in selection of chemoresistant patients. Breast Cancer Res Treat 19: 85–93
Noonan KE, Beck C and Holzmayer TA (1990) Quantitative analysis of MDR1(multidrug resistance) gene expression in human tumors by polymerase chain reaction. Proc Natl Acad Sci USA 87: 7160–7164
Nooter K, Brutel de la Riviere G, Look MP, Van Wingerden KE, Henzen-Logmans SC, Scheper RJ, Flens MJ, Klijn JGM, Stoter G and Foekens JA (1997) The prognostic significance of expression of the multidrug resistance associated protein (MRP) in primary breast cancer. Br J Cancer 76: 486–493
Pastan I and Gottesman MM (1987) Multiple-drug resistance in human cancer. N Engl J Med 316: 1388–1393
Raybaud-Diogène H, Tétu B, Morency R, Fortin A and Monteil RA (1996) P53 overexpression in head and neck squamous cell carcinoma: review of the literature. Oral Oncol, Eur J Cancer 32B: 143–149
Remvikos Y, Beuzedoc P, Zajdela A, Voillemot N, Magdelenat H and Pouillart P (1989) Correlation of pretreatment proliferative activity of breast cancer with the response to cytotoxic chemotherapy. J Natl Cancer Inst 81: 1383–1387
Romain S, Formento JL, Guirou O, Francoual M, Milano G and Martin PM (1994) Determination of oestrogen receptors by enzyme immunoassay. Technical differences between laboratories and their consequences. Eur J Cancer 30: 740–746
Scarff RW and Torloni H (1968). Histological typing of breast tumors, Geneva: World Health Organization: 13–20
Shimamura A and Fisher DE (1996) P53 in life and death. Clin Cancer Res 2: 435–440
Silvestrini R, Benini E, Veneroni S, Daidone MG, Tomasic G, Squicciarini P and Salvadori B (1996) P53 and bcl-2 expression correlates with clinical outcome in a series of node-positive breast cancer patients. J Clin Oncol 14: 1604–1610
Tannock IF (1998) Conventional cancer therapy: promise broken or promise delayed. Lancet 351: 9–16
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Ferrero, J., Etienne, M., Formento, J. et al. Application of an original RT-PCR–ELISA multiplex assay for MDR1 and MRP, along with p53 determination in node-positive breast cancer patients. Br J Cancer 82, 171–177 (2000). https://doi.org/10.1054/bjoc.1999.0896
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1054/bjoc.1999.0896
Keywords
This article is cited by
-
A novel nanoparticle formulation overcomes multiple types of membrane efflux pumps in human breast cancer cells
Drug Delivery and Translational Research (2012)
-
Prognostic impact of multidrug resistance gene expression on the management of breast cancer in the context of adjuvant therapy based on a series of 171 patients
British Journal of Cancer (2006)
-
Expression of multidrug resistance-associated protein1,P-glycoprotein, and thymidylate synthase in gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection
British Journal of Cancer (2002)