title: Application of an original RT-PCR-ELISA multiplex assay for MDR1 and MRP, along with p53 determination in node-positive breast cancer patients.
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 (beta2-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).
authors.affiliation: Centre Antoine Lacassagne, Oncopharmacology Unit, Nice, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Ferrero
authors.forename: M C
authors.initials: MC
authors.lastname: Etienne
authors.forename: J L
authors.initials: JL
authors.lastname: Formento
authors.forename: M
authors.initials: M
authors.lastname: Francoual
authors.forename: P
authors.initials: P
authors.lastname: Rostagno
authors.forename: I
authors.initials: I
authors.lastname: Peyrottes
authors.forename: F
authors.initials: F
authors.lastname: Ettore
authors.forename: E
authors.initials: E
authors.lastname: Teissier
authors.forename: P
authors.initials: P
authors.lastname: Leblanc-Talent
authors.forename: M
authors.initials: M
authors.lastname: Namer
authors.forename: G
authors.initials: G
authors.lastname: Milano
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*; D012680:Sensitivity and Specificity; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53