Expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) is an independent prognostic indicator of worse outcome in gastric cancer patients

被引:210
作者
Lieto, Eva [1 ]
Ferraraccio, Francesca [2 ]
Orditura, Michele [3 ]
Castellano, Paolo [1 ]
La Mura, Anna [2 ]
Pinto, Margherita [1 ]
Zamboli, Anna [1 ]
DeVita, Ferdinando [3 ]
Galizia, Gennaro [1 ]
机构
[1] Univ Naples 2, Sch Med, Policlin 2,F Margrassi A Lanzara Dept Clin & Expt, Div Surg Oncol, I-80131 Naples, Italy
[2] Univ Naples 2, Sch Med, Policlin 2,F Margrassi A Lanzara Dept Clin & Expt, Div Pathol, I-80131 Naples, Italy
[3] Univ Naples 2, Sch Med, Policlin 2,F Margrassi A Lanzara Dept Clin & Expt, Div Med Oncol, I-80131 Naples, Italy
关键词
gastric cancer; prognostic factors; vascular endothelial growth factor; epidermal growth factor receptor; targeted biological therapy;
D O I
10.1245/s10434-007-9596-0
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Unlike other human tumors, gastric cancer remains a great therapeutic challenge since no standardized postoperative treatment exists. Knowledge of molecular pathways determining the behavior of individual gastric tumors seems to be crucial for therapeutic decisions, and evaluation of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expression might be critical for prognosis, assessment, and identification of patients that could be treated with tailored therapies. Methods: VEGF and EGFR determination was performed in 88 gastric cancer samples as well as 25 normal gastric mucosa specimens from non-cancer patients using a commercially available immunohistochemistry kit. In all samples, the correlation of VEGF and EGFR expression was investigated with each other, and with other prognostic indicators in all samples, and, finally, with survival rates in 69 patients undergoing potentially curative surgery. Results: Forty-eight per cent (42 cases) of gastric cancers expressed VEGF, and 44% (39 cases) stained for EGFR. In curatively treated patients, VEGF and EGFR expression was demonstrated to correlate with worse survival in both univariate and multivariate analyses. Molecular profiling was shown to more accurately estimate the risk of cancer-related death than TNM stage, and, of most interest, to allow sorting out high-risk patients within the same stage. Conclusions: These findings provide evidence that contemporary evaluation of VEGF and EGFR expression may be crucial to select gastric cancer patients with poor prognosis who may benefit of tailored treatments.
引用
收藏
页码:69 / 79
页数:11
相关论文
共 38 条
[21]   Expression of Cbl linking with the epidermal growth factor receptor system is associated with tumor progression and poor prognosis of human gastric carcinoma [J].
Ito, R ;
Nakayama, H ;
Yoshida, K ;
Matsumura, S ;
Oda, N ;
Yasui, W .
VIRCHOWS ARCHIV, 2004, 444 (04) :324-331
[22]   Cancer statistics, 2006 [J].
Jemal, A ;
Siegel, R ;
Ward, E ;
Murray, T ;
Xu, JQ ;
Smigal, C ;
Thun, MJ .
CA-A CANCER JOURNAL FOR CLINICIANS, 2006, 56 (02) :106-130
[23]   Vascular endothelial growth factor-D and its receptor VEGFR-3:: Two novel independent prognostic markers in gastric adenocarcinoma [J].
Jüttner, S ;
Wissmann, C ;
Jöns, T ;
Vieth, M ;
Hertel, J ;
Gretschel, S ;
Schlag, PM ;
Kemmner, W ;
Höcker, M .
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (02) :228-240
[24]   An observational study suggesting clinical benefit for adjuvant postoperative chemoradiation in a population of over 500 cases after gastric resection with D2 nodal dissection for adenocarcinoma of the stomach [J].
Kim, S ;
Lim, DH ;
Lee, J ;
Kang, WK ;
MacDonald, JS ;
Park, CH ;
Park, SH ;
Lee, SH ;
Kim, K ;
Park, JO ;
Kim, WS ;
Jung, CW ;
Park, YS ;
Im, YH ;
Sohn, TS ;
Noh, JH ;
Heo, JS ;
Kim, YI ;
Park, CK ;
Park, K .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2005, 63 (05) :1279-1285
[25]   VEGF-C and VEGF-A synergistically enhance lymph node metastasis of gastric cancer [J].
Kondo, Kenji ;
Kaneko, Takeshi ;
Baba, Megumi ;
Konno, Hiroyuki .
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 2007, 30 (04) :633-637
[26]   Inhibition of heat shock protein 90 impairs epidermal growth factor-mediated signaling in gastric cancer cells and reduces tumor growth and vascularization in vivo [J].
Lang, Sven A. ;
Klein, Dagmar ;
Moser, Christian ;
Gaumann, Andreas ;
Glockzin, Gabriel ;
Dahlke, Marc H. ;
Dietmaier, Wolfgang ;
Bolder, Ulrich ;
Schlitt, Hans J. ;
Geissler, Edward K. ;
Stoeltzing, Oliver .
MOLECULAR CANCER THERAPEUTICS, 2007, 6 (03) :1123-1132
[27]   Gastric cancer - New therapeutic options [J].
Macdonald, John S. .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (01) :76-77
[28]  
McCarty MF, 2004, MOL CANCER THER, V3, P1041
[29]   Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer [J].
Mendelsohn, J ;
Baselga, J .
JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (14) :2787-2799
[30]   Predicting individual survival after gastric cancer resection - Validation of a US-derived nomogram at a single high-volume center in Europe [J].
Novotny, AR ;
Schuhmacher, C ;
Busch, R ;
Kattan, MW ;
Brennan, MF ;
Siewert, JR .
ANNALS OF SURGERY, 2006, 243 (01) :74-81