Investigation of MRP-1 protein and MDR-1 P-glycoprotein expression in invasive breast cancer: a prognostic study.
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.
Larkin
Annemarie
A
National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
O'Driscoll
Lorraine
L
Kennedy
Susan
S
Purcell
Rachel
R
Moran
Elizabeth
E
Crown
John
J
Parkinson
Michael
M
Clynes
Martin
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis*; D011379:Prognosis; D012189:Retrospective Studies
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C421109:multidrug resistance-associated protein 1