The clinical role of the PEA3 transcription factor in ovarian and breast carcinoma in effusions

被引:29
作者
Davidson, B
Goldberg, I
Tell, L
Vigdorchik, S
Baekelandt, M
Berner, A
Kristensen, GB
Reich, R
Kopolovic, J
机构
[1] Univ Oslo, Dept Pathol, Norwegian Radium Hosp, Oslo, Norway
[2] Sheba Med Ctr, Dept Pathol, Tel Hashomer, Israel
[3] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel
[4] Hebrew Univ Jerusalem, Fac Med, Dept Pharmacol & Expt Therapeut, Jerusalem, Israel
[5] Norwegian Radium Hosp, Dept Gynecol Oncol, Oslo, Norway
[6] Hebrew Univ Jerusalem, David R Bloom Ctr Pharm, IL-91905 Jerusalem, Israel
关键词
Ets transcription factors; mRNA in situ hybridization; serous effusions; metastasis;
D O I
10.1023/B:CLIN.0000037703.37275.35
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Ets transcription factors play a central role in invasion and metastasis through regulation of synthesis of proteolytic enzymes and angiogenic molecules. The objective of this study was to investigate the role of PEA3 in tumor progression of ovarian and breast carcinoma metastatic to effusions, and to evaluate the expression of Ets-2 and Erg in ovarian carcinoma. Ovarian (83 malignant effusions, 102 corresponding solid lesions) and breast (33 malignant effusions, 40 corresponding solid lesions) carcinomas were evaluated for expression of PEA3 using mRNA in situ Hybridization (ISH). Expression of Ets-2 and Erg mRNA was analyzed in 50 ovarian carcinoma effusions using the same method. PEA3 mRNA expression was comparable at all sites in ovarian carcinoma (44 out of 83; 53% of effusions, 48 out of 102; 47% of solid tumors). PEA3 mRNA expression in effusions correlated with mRNA expression of the previously studied alphaV (P=0.022), alpha6 (P<0.001) and beta 1 (P<0.001) integrin subunits, the matrix metalloproteinase (MMP) inducer EMMPRIN (P=0.015) and interleukin-8 (IL-8) ( P=0.033). Erg and Ets-2 mRNA was expressed in 15 out of 50 (30%) and 18 out of 50 (36%) effusions, respectively, and co-localized with PEA3 (P=0.017 for Erg, P=0.004 for Ets-2). In breast carcinoma, PEA3 expression was seen in 19/40 (48%) of solid lesions, with a significant upregulation in corresponding effusions compared to primary tumors (24 out of 33; 73%, P=0.038). PEA3 mRNA expression in effusions obtained prior to the institution of chemotherapy predicted significantly shorter overall survival in univariate analysis (24 vs 37 months, P=0.03), with a similar trend for Erg (13 vs 30 months, P=0.1). In conclusion, PEA3 is expressed at all anatomic sites in serous ovarian cancer and co-localizes with Erg, Ets-2 and several metastasis-associated molecules. PEA3 mRNA expression is a novel marker for tumor progression to malignant effusion in breast carcinoma, and predicts poor outcome in effusions sampled prior to therapeutic intervention in ovarian carcinoma. These findings support a biological role for Ets transcription factors in these malignancies and suggests that they may be targets for therapeutic intervention.
引用
收藏
页码:191 / 199
页数:9
相关论文
共 56 条
[31]   Expression of E1AF/PEA3, an ETS-related transcription factor in human non-small-cell lung cancers: Its relevance in cell motility and invasion [J].
Hiroumi, H ;
Dosaka-Akita, H ;
Yoshida, K ;
Shindoh, M ;
Ohbuchi, T ;
Fujinaga, K ;
Nishimura, M .
INTERNATIONAL JOURNAL OF CANCER, 2001, 93 (06) :786-791
[32]  
HORWITZ VG, 2003, CLIN EXP METASTAS, V20, P599
[33]   PEA3 and AP-1 are required for constitutive IL-8 gene expression in hepatoma cells [J].
Iguchi, A ;
Kitajima, I ;
Yamakuchi, M ;
Ueno, S ;
Aikou, T ;
Kubo, T ;
Matsushima, K ;
Mukaida, N ;
Maruyama, I .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 279 (01) :166-171
[34]  
Ito Y, 2002, ANTICANCER RES, V22, P1581
[35]  
Ito Y, 2002, ANTICANCER RES, V22, P2385
[36]   Cancer statistics, 2003 [J].
Jemal, A ;
Murray, T ;
Samuels, A ;
Ghafoor, A ;
Ward, E ;
Thun, MJ .
CA-A CANCER JOURNAL FOR CLINICIANS, 2003, 53 (01) :5-26
[37]   Clinical significance of PEA3 in human breast cancer [J].
Kinoshita, J ;
Kitamura, K ;
Tanaka, S ;
Sugimachi, K ;
Ishida, M ;
Saeki, H .
SURGERY, 2002, 131 (01) :S222-S225
[38]   INVOLVEMENT OF A MITOGEN-ACTIVATED PROTEIN-KINASE SIGNALING PATHWAY IN THE REGULATION OF UROKINASE PROMOTER ACTIVITY BY C-HA-RAS [J].
LENGYEL, E ;
STEPP, E ;
GUM, R ;
BOYD, D .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (39) :23007-23012
[39]  
MONTE D, 1995, ONCOGENE, V11, P771
[40]  
MONTE D, 1994, ONCOGENE, V9, P1397