PARP-1 expression in breast cancer including BRCA1-associated, triple negative and basal-like tumors: possible implications for PARP-1 inhibitor therapy

被引:101
作者
Domagala, Pawel [3 ]
Huzarski, Tomasz [3 ]
Lubinski, Jan [3 ]
Gugala, Karol [2 ]
Domagala, Wenancjusz [1 ]
机构
[1] Pomeranian Med Univ, Dept Pathol, PL-71242 Szczecin, Poland
[2] Reg Oncol Hosp, Dept Pathol, PL-10561 Olsztyn, Poland
[3] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, PL-70115 Szczecin, Poland
关键词
Breast cancer; PARP-1; BRCA1; Basal-like; Triple negative; POLY(ADP-RIBOSE) POLYMERASE; STRATEGY; CELLS;
D O I
10.1007/s10549-011-1441-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Despite ongoing trials of PARP inhibitors in the treatment of breast cancer (BC), the extent of poly(ADP-ribose)polymerase-1 (PARP-1) protein expression in BCs, which may influence treatment results, is not known. The purpose of this report is to assess expression of PARP-1 in BC including BRCA1-associated, triple negative (TN), and basal-like tumors. Immunohistochemistry with a PARP-1 antibody on tissue microarrays from 130 BRCA1-associated and 594 BRCA1-non-related BCs was used. The vast majority of breast carcinomas expressed high level of nuclear PARP-1 protein and a small percentage of tumors exhibited both nuclear and cytoplasmic PARP-1 expression. There was a significant difference between the mean nuclear PARP-1 quickscore in BRCA1-associated versus BRCA1-non-associated carcinomas in all tumors (P < 0.0001), in the basal-like group (P = 0.0086), TN (P = 0.0015), and non-basal-like groups (P = 0.016) but not in the non-TN group. Among BRCA1-associated BCs, low PARP-1 expression was found in 18.5% of all cases, 18.9% of basal-like and 21% of TN cancers. Among BRCA1-non-related tumors, low PARP-1 expression was found in 8.8% of all cases, 3.1% of basal-like, and 2.7% of TN cancers. PARP-1 expression is significantly associated with BRCA1 status in basal-like and TN BCs. The assessment of PARP-1 expression in tumor samples may improve the selection of BC patients for PARP inhibitor therapy.
引用
收藏
页码:861 / 869
页数:9
相关论文
共 24 条
[1]  
Bieche I, 1996, CLIN CANCER RES, V2, P1163
[2]   Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase [J].
Bryant, HE ;
Schultz, N ;
Thomas, HD ;
Parker, KM ;
Flower, D ;
Lopez, E ;
Kyle, S ;
Meuth, M ;
Curtin, NJ ;
Helleday, T .
NATURE, 2005, 434 (7035) :913-917
[3]   Basal-like breast cancer defined by five biomarkers has superior prognostic value then triple-negative phenotype [J].
Cheang, Maggie C. U. ;
Voduc, David ;
Bajdik, Chris ;
Leung, Samuel ;
McKinney, Steven ;
Chia, Stephen K. ;
Perou, Charles M. ;
Nielsen, Torsten O. .
CLINICAL CANCER RESEARCH, 2008, 14 (05) :1368-1376
[4]  
Comen EA, 2010, ONCOLOGY-NY, V24, P55
[5]   RETRACTED: Poly(Adenosine Diphosphate-Ribose) Polymerase-1 Expression in Cutaneous Malignant Melanomas as a New Molecular Marker of Aggressive Tumor (Retracted Article) [J].
Csete, Bela ;
Lengyel, Zsuzsanna ;
Kadar, Zsolt ;
Battyani, Zita .
PATHOLOGY & ONCOLOGY RESEARCH, 2009, 15 (01) :47-53
[6]   A QUICKSCORE METHOD FOR IMMUNOHISTOCHEMICAL SEMIQUANTITATION - VALIDATION FOR ESTROGEN-RECEPTOR IN BREAST CARCINOMAS [J].
DETRE, S ;
JOTTI, GS ;
DOWSETT, M .
JOURNAL OF CLINICAL PATHOLOGY, 1995, 48 (09) :876-878
[7]   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
[8]   Selective inhibition of BRCA2-deficient mammary tumor cell growth by AZD2281 and cisplatin [J].
Evers, Bastiaan ;
Drost, Rinske ;
Schut, Eva ;
de Bruin, Michiel ;
van der Burg, Eline ;
Derksen, Patrick W. B. ;
Holstege, Henne ;
Liu, Xiaoling ;
van Drunen, Ellen ;
Beverloo, H. Berna ;
Smith, Graeme C. M. ;
Martin, Niall M. B. ;
Lau, Alan ;
O'Connor, Mark J. ;
Jonkers, Jos .
CLINICAL CANCER RESEARCH, 2008, 14 (12) :3916-3925
[9]   Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy [J].
Farmer, H ;
McCabe, N ;
Lord, CJ ;
Tutt, ANJ ;
Johnson, DA ;
Richardson, TB ;
Santarosa, M ;
Dillon, KJ ;
Hickson, I ;
Knights, C ;
Martin, NMB ;
Jackson, SP ;
Smith, GCM ;
Ashworth, A .
NATURE, 2005, 434 (7035) :917-921
[10]   Inhibition of Poly(ADP-Ribose) Polymerase in Tumors from BRCA Mutation Carriers. [J].
Fong, Peter C. ;
Boss, David S. ;
Yap, Timothy A. ;
Tutt, Andrew ;
Wu, Peijun ;
Mergui-Roelvink, Marja ;
Mortimer, Peter ;
Swaisland, Helen ;
Lau, Alan ;
O'Connor, Mark J. ;
Ashworth, Alan ;
Carmichael, James ;
Kaye, Stan B. ;
Schellens, Jan H. M. ;
de Bono, Johann S. .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (02) :123-134