Type

Journal Article

Authors

Martin Clynes
Michael Parkinson
John Crown
Elizabeth Moran
Rachel Purcell
Susan Kennedy
Lorraine O'Driscoll
Annemarie Larkin

Subjects

Microbiology

Topics
prognosis female genetics multidrug resistance associated protein 1 multidrug resistance associated proteins retrospective studies aged biosynthesis pathology drug resistance neoplasm disease free survival humans middle aged p glycoprotein gene expression regulation breast neoplasms immunohistochemistry

Investigation of MRP-1 protein and MDR-1 P-glycoprotein expression in invasive breast cancer: a prognostic study. (2004)

Abstract The efficacy of breast cancer treatment is limited by the development of resistance to various chemotherapeutic agents. We conducted a retrospective study of the expression of 2 drug resistance efflux pumps, MRP-1 and MDR-1 Pgp, in 177 invasive breast carcinomas. Immunohistochemical expression of these proteins was correlated with clinicopathologic characteristics as well as relapse-free survival (RFS) and overall survival (OS) times. MDR-1 Pgp was associated strongly with higher histologic grade (grade III). A highly significant association was shown between MDR-1 Pgp and MRP-1 expression (p < 0.01), 47.4% of patients expressing both proteins; MRP-1 was expressed in approximately 61% of patients and MDR-1, in approximately 66% of patients. No association was shown in the overall group between either MDR-1 Pgp or MRP-1 and any of the other clinicopathologic features. Kaplan-Meier analysis revealed that in a subset of patients with either high-grade (grade III) stage 1 (node-negative) or stage 2 (node-positive) tumours who were treated with surgery followed by adjuvant chemotherapy, MRP-1 expression in <25% of tumour cells at diagnosis was significantly associated with improved RFS (p < 0.02) and OS (p < 0.02). Using multivariate analysis, MRP-1 expression in <25% of tumour cells at diagnosis was identified as an independent, significant prognostic factor for RFS (p < 0.01) and OS (p < 0.01) in this patient group but not in other groups. In this subgroup, no significant correlation was observed between expression of MDR-1 Pgp and MRP-1. While the number of patients with high-grade tumours treated with adjuvant chemotherapy was small and further confirmatory research is warranted, it appears that assessment of MRP-1 expression at diagnosis may offer useful prognostic information in subgroups of patients with stage 1 or stage 2 high-grade tumours who receive CMF-based adjuvant chemotherapy. Given the known substrate specificities of MRP-1, any mechanistic relationship between MRP-1 expression and CMF resistance remains unclear. No association was shown between MDR-1 Pgp expression and either RFS or OS time in any subgroup of patients.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

Martin Clynes, Michael Parkinson, John Crown, Elizabeth Moran, Rachel Purcell, Susan Kennedy, Lorraine O'Driscoll, Annemarie Larkin

Experts in our system

1
Martin Clynes
Dublin City University
Total Publications: 209
 
2
John Crown
Dublin City University
 
3
Susan Kennedy
Dublin City University
Total Publications: 37
 
4
Lorraine O'Driscoll
Trinity College Dublin
Total Publications: 152
 
5
Annemarie Larkin
Dublin City University
Total Publications: 25