Prognostic significance of the immunohistochemical expression of O6-methylguanine-DNA methyltransferase, P-glycoprotein, and multidrug resistance protein-1 in glioblastomas

被引:30
作者
Nakagawa, Takao [1 ]
Ido, Kazunori [1 ]
Sakuma, Takahiro [1 ]
Takeuchi, Hiroaki [1 ]
Sato, Kazufumi [1 ]
Kubota, Toshihiko [1 ]
机构
[1] Univ Fukui, Fac Med Sci, Dept Neurosurg, Eiheiji, Fukui 9101193, Japan
基金
日本学术振兴会;
关键词
glioblastoma; immunohistochemistry; MRP-1; O-6-MGMT; P-glycoprotein; prognosis; PROMOTER HYPERMETHYLATION; DRUG-RESISTANCE; METHYLATION; SURVIVAL; GENE; RADIOTHERAPY; TEMOZOLOMIDE; MULTIFORME; MARKERS; GLIOMAS;
D O I
10.1111/j.1440-1789.2008.00983.x
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
We studied the expression of O-6-methylguanine-DNA methyltransferase (O-6-MGMT), P-glycoprotein (Pgp), and multidrug resistance protein-1 (MRP-1) in 23 glioblastomas using RT-PCR, methylation-specific PCR, and immunohistochemistry, and analyzed their association with overall patient survival. Univariate analysis of collected data demonstrated that the expressions of O-6-MGMT and MRP-1 detected by immunohistochemistry, in addition to the consistent factors, including preoperative Karnofsky performance scale (KPS), radical surgery, and tumor location and extension, were significant prognostic factors for the overall survival (OS) of patients with glioblastoma, who received nimustine (ACNU)-based chemotherapy in association with surgery and radiotherapy. Among them, following multivariate analysis, preoperative KPS, radical surgery, tumor location, and the expression of O-6-MGMT remained as significant prognostic factors. These findings suggest that immunohistochemical analysis of O-6-MGMT in patients with glioblastoma can be a useful method to predict the effects of chemotherapy and identify alternative chemotherapeutic regimens for O-6-MGMT-positive patients.
引用
收藏
页码:379 / 388
页数:10
相关论文
共 18 条
[1]   Relationship between expression of O6-methylguanine-DNA methyltransferase, glutathione-S-transferase, π in glioblastoma and the survival of the patients treated with nimustine hydrochloride:: An immunohistochemical analysis [J].
Anda, T ;
Shabani, HK ;
Tsunoda, K ;
Tokunaga, Y ;
Kaminogo, M ;
Shibata, S ;
Hayashi, T ;
Iseki, M .
NEUROLOGICAL RESEARCH, 2003, 25 (03) :241-248
[2]  
Andersson U, 2004, CLIN NEUROPATHOL, V23, P21
[3]  
Belanich M, 1996, CANCER RES, V56, P783
[4]   Correlation of clinical features and methylation status of MGMT gene promoter in glioblastomas [J].
Blanc, JL ;
Wager, M ;
Guilhot, J ;
Kusy, S ;
Bataille, B ;
Chantereau, T ;
Lapierre, F ;
Larsen, CJ ;
Karayan-Tapon, L .
JOURNAL OF NEURO-ONCOLOGY, 2004, 68 (03) :275-283
[5]   Brain-tumour drug resistance: the bare essentials [J].
Bredel, M ;
Zentner, J .
LANCET ONCOLOGY, 2002, 3 (07) :397-406
[6]   Prognostic significance of O6-methylguanine-DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression in anaplastic gliomas [J].
Brell, M ;
Tortosa, A ;
Verger, E ;
Gil, JM ;
Viñolas, N ;
Villá, S ;
Acebes, JJ ;
Caral, L ;
Pujol, T ;
Ferrer, I ;
Ribalta, T ;
Graus, F .
CLINICAL CANCER RESEARCH, 2005, 11 (14) :5167-5174
[7]   A simplified laboratory validated assay for MGMT promoter hypermethylation analysis of glioma specimens from formalin-fixed paraffin-embedded tissue [J].
Cankovic, Milena ;
Mikkelsen, Tom ;
Rosenblum, Mark L. ;
Zarbo, Richard J. .
LABORATORY INVESTIGATION, 2007, 87 (04) :392-397
[8]   MGMT prognostic impact on glioblastoma is dependent on therapeutic modalities [J].
Criniere, Emmanuelle ;
Kaloshi, Gentian ;
Laigle-Donadey, Florence ;
Lejeune, Julie ;
Auger, Nathalie ;
Benouaich-Amiel, Alexandra ;
Everhard, Sibille ;
Mokhtari, Karima ;
Polivka, Marc ;
Delattre, Jean-Yves ;
Hoang-Xuan, Khe ;
Thillet, Joelle ;
Sanson, Marc .
JOURNAL OF NEURO-ONCOLOGY, 2007, 83 (02) :173-179
[9]  
Esteller M, 1999, CANCER RES, V59, P793
[10]   Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide [J].
Hegi, ME ;
Diserens, AC ;
Godard, S ;
Dietrich, PY ;
Regli, L ;
Ostermann, S ;
Otten, P ;
Van Melle, G ;
de Tribolet, N ;
Stupp, R .
CLINICAL CANCER RESEARCH, 2004, 10 (06) :1871-1874