ERCC1, hRad51, and BRCA1 protein expression in relation to tumour response and survival of stage III/IV NSCLC patients treated with chemotherapy

被引:171
作者
Wachters, FM
Wong, LSM
Timens, W
Kampinga, HH
Groen, HJM
机构
[1] Univ Groningen Hosp, Dept Pulm Dis, NL-9700 RB Groningen, Netherlands
[2] Univ Groningen, Dept Radiat & Stress Cell Biol, NL-9713 AV Groningen, Netherlands
[3] Univ Groningen Hosp, Dept Pathol & Lab Med, NL-9700 RB Groningen, Netherlands
关键词
BRCA1; chemotherapy; ERCC1; gemcitabine; homologous recombination; hRad51; non-small-cell lung cancer; nucleotide excision repair;
D O I
10.1016/j.lungcan.2005.06.013
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Aim of this explorative study was to determine the prognostic value of protein expression of the DNA damage repair enzymes ERCC1, hRad51, and BRCA1 for tumour response and survival of non-small-cell lung cancer patients treated with chemotherapy. Patients with either a short or long overall survival were selected from a randomized phase III trial comparing cisplatin-gemcitabine and epirubicin-gemcitabine. Tumour biopsies were assessed for differences in immunohistochemical staining using antibodies against ERCC1, hRad51, and BRCA1. A total of 33 patients were included. A positive nuclear staining for ERCC1, hRad51, and BRCA1 was observed in 44, 12, and 90% of biopsies, respectively. In large cell carcinoma nuclear hRad51 staining was absent. In five biopsies stained for hRad51 an unexpected membrane-like staining was observed; these biopsies showed no nuclear staining. DNA damage repair protein expressions were not significantly different in responders versus non-responders, or in patients with a short or long overall survival. In conclusion, immunohistochemical staining of ERCC1, hRad51, and BRCA1, in tumour biopsies from non-small-cell lung cancer patients was not predictive for tumour response and survival after chemotherapy. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:211 / 219
页数:9
相关论文
共 40 条
[1]
SINGLE-AGENT ACTIVITY OF WEEKLY GEMCITABINE IN ADVANCED NON-SMALL-CELL LUNG-CANCER - A PHASE-II STUDY [J].
ANDERSON, H ;
LUND, B ;
BACH, F ;
THATCHER, N ;
WALLING, J ;
HANSEN, HH .
JOURNAL OF CLINICAL ONCOLOGY, 1994, 12 (09) :1821-1826
[2]
MUTAGENICITY AND CARCINOGENICITY OF TOPOISOMERASE-INTERACTIVE AGENTS [J].
ANDERSON, RD ;
BERGER, NA .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 1994, 309 (01) :109-142
[3]
Bergman AM, 1996, CLIN CANCER RES, V2, P521
[4]
The breast cancer susceptibility gene BRCA1 is required for subnuclear assembly of Rad51 and survival following treatment with the DNA cross-linking agent cisplatin [J].
Bhattacharyya, A ;
Ear, US ;
Koller, BH ;
Weichselbaum, RR ;
Bishop, DK .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (31) :23899-23903
[5]
Bosken CH, 2002, JNCI-J NATL CANCER I, V94, P1091
[6]
Prognostic factors in non-small cell lung cancer - A decade of progress [J].
Brundage, MD ;
Davies, D ;
Mackillop, WJ .
CHEST, 2002, 122 (03) :1037-1057
[7]
DNA repair mechanisms involved in gemcitabine cytotoxicity and in the interaction between gemcitabine and cisplatin [J].
Crul, M ;
van Waardenburg, RCAM ;
Bocxe, S ;
van Eijndhoven, MAJ ;
Pluim, D ;
Beijnen, JH ;
Schellens, JHM .
BIOCHEMICAL PHARMACOLOGY, 2003, 65 (02) :275-282
[8]
The XRCC2 and XRCC3 repair genes are required for chromosome stability in mammalian cells [J].
Cui, X ;
Brenneman, M ;
Meyne, J ;
Oshimura, M ;
Goodwin, EH ;
Chen, DJ .
MUTATION RESEARCH-DNA REPAIR, 1999, 434 (02) :75-88
[9]
ERCC1 AND ERCC2 EXPRESSION IN MALIGNANT-TISSUES FROM OVARIAN-CANCER PATIENTS [J].
DABHOLKAR, M ;
BOSTICKBRUTON, F ;
WEBER, C ;
BOHR, VA ;
EGWUAGU, C ;
REED, E .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1992, 84 (19) :1512-1517
[10]
Defining the roles of nucleotide excision repair and recombination in the repair of DNA interstrand cross-links in mammalian cells [J].
De Silva, IU ;
McHugh, PJ ;
Clingen, PH ;
Hartley, JA .
MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (21) :7980-7990