Investigation of MRP-1 protein and MDR-1 P-glycoprotein expression in invasive breast cancer: A prognostic study

被引:70
作者
Larkin, A [1 ]
O'Driscoll, L
Kennedy, S
Purcell, R
Moran, E
Crown, J
Parkinson, M
Clynes, M
机构
[1] Dublin City Univ, Natl Inst Cellular Biotechnol, Dublin 9, Ireland
[2] Royal Victorian Eye & Ear Hosp, Dept Pathol, Dublin, Ireland
[3] St Vincents Univ Hosp, Dept Pathol, Dublin, Ireland
[4] St Vincents Univ Hosp, Dept Med Oncol, Dublin, Ireland
[5] Dublin City Univ, Sch Biotechnol, Dublin 9, Ireland
关键词
breast cancer; MRP-1; MDR-1; Pgp; immunohistochemistry; prognosis; relapse-free survival; overall survival;
D O I
10.1002/ijc.20369
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 I (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 I 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. (C) 2004 Wiley-Liss, Inc.
引用
收藏
页码:286 / 294
页数:9
相关论文
共 34 条
[1]   Neoadjuvant therapy in breast cancer: Can we define its role? [J].
Aapro, MS .
ONCOLOGIST, 2001, 6 :36-39
[2]   Multiple gene expression analysis reveals distinct differences between G2 and G3 stage breast cancers, and correlations of PKCη with MDR1, MRP and LRP gene expression [J].
Beck, J ;
Bohnet, B ;
Brügger, D ;
Bader, P ;
Dietl, J ;
Scheper, RJ ;
Kandolf, R ;
Liu, C ;
Niethammer, D ;
Gekeler, V .
BRITISH JOURNAL OF CANCER, 1998, 77 (01) :87-91
[3]   MRP8, a new member of ABC transporter superfamily, identified by EST database mining and gene prediction program, is highly expressed in breast cancer [J].
Bera, TK ;
Lee, S ;
Salvatore, G ;
Lee, B ;
Pastan, I .
MOLECULAR MEDICINE, 2001, 7 (08) :509-516
[4]   QUANTITATIVE IMMUNOCYTOCHEMICAL ASSAYS OF P-GLYCOPROTEIN IN BREAST CARCINOMAS - CORRELATION TO MESSENGER-RNA EXPRESSION AND TO IMMUNOHISTOCHEMICAL PROGNOSTIC INDICATORS [J].
CHARPIN, C ;
VIELH, P ;
DUFFAUD, F ;
DEVICTOR, B ;
ANDRAC, L ;
LAVAUT, MN ;
ALLASIA, C ;
HORSCHOWSKI, N ;
PIANA, L .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1994, 86 (20) :1539-1545
[5]  
Chevillard S, 1996, CANCER, V77, P292, DOI 10.1002/(SICI)1097-0142(19960115)77:2<292::AID-CNCR11>3.0.CO
[6]  
2-X
[7]  
CLYNES SP, 1992, SCIENCE, V258, P1605
[8]  
Dexter DW, 1998, CLIN CANCER RES, V4, P1533
[9]   A multidrug resistance transporter from human MCF-7 breast cancer cells [J].
Doyle, LA ;
Yang, WD ;
Abruzzo, LV ;
Krogmann, T ;
Gao, YM ;
Rishi, AK ;
Ross, DD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (26) :15665-15670
[10]   PATHOLOGICAL PROGNOSTIC FACTORS IN BREAST-CANCER .1. THE VALUE OF HISTOLOGICAL GRADE IN BREAST-CANCER - EXPERIENCE FROM A LARGE STUDY WITH LONG-TERM FOLLOW-UP [J].
ELSTON, CW ;
ELLIS, IO .
HISTOPATHOLOGY, 1991, 19 (05) :403-410