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Vascular endothelial growth factor-D and its receptor VEGFR-3: Two novel independent prognostic markers in gastric adenocarcinoma

Official URL:https://doi.org/10.1200/JCO.2004.00.3467
PubMed:View item in PubMed
Creators Name:Juettner, S. and Wissmann, C. and Joens, T. and Vieth, M. and Hertel, J. and Gretschel, S. and Schlag, P.M. and Kemmner, W. and Hoecker, M.
Journal Title:Journal of Clinical Oncology
Journal Abbreviation:J Clin Oncol
Volume:24
Number:2
Page Range:228-240
Date:10 January 2006
Keywords:Adenocarcinoma, Disease-Free Survival, Immunohistochemistry, Lymphatic Metastasis, Messenger RNA, Prognosis, Stomach Neoplasms, Tumor Cell Line, Vascular Endothelial Growth Factor C, Vascular Endothelial Growth Factor D, Vascular Endothelial Growth Factor Receptor-3
Abstract:PURPOSE: Vascular endothelial growth factor (VEGF)-D and its homolog VEGF-C influence lymphangiogenesis through activation of VEGF receptor 3 (VEGFR-3), and have been implicated in lymphatic tumor spread. Nodal dissemination of gastric adenocarcinomas critically determines clinical outcome and therapeutic options of affected patients. Therefore, we analyzed expression and prognostic significance of VEGF-D along with VEGF-C, and VEGFR-3 in gastric adenocarcinomas. MATERIALS AND METHODS: VEGF-C, VEGF-D, and VEGFR-3 were analyzed in 91 R(0)-resected primary gastric adenocarcinomas, corresponding noncancerous gastric mucosa, and lymph node metastases employing immunohistochemistry and/or in situ hybridization. Blood and lymph vessel densities were assessed after staining with CD31 and LYVE-1-specific antibodies. RESULTS: VEGF-D and VEGF-C were detected in 67.0% and 50.5% of gastric cancers, respectively. Healthy gastric mucosa was negative for VEGF-C and in 12.5% positive for VEGF-D. Presence of VEGF-D (P = .005) or VEGF-C (P = .006) was correlated with lymphatic metastases and decreased survival (VEGF-D, P < .05; VEGF-C, P < .05). VEGFR-3 was correlated with reduced carcinoma-specific survival (P < .05), and Cox multivariate regression analysis qualified VEGF-D and VEGFR-3, but not VEGF-C, as independent prognostic parameters. In lymph node-positive gastric cancers, presence of VEGF-D/VEGFR-3 was associated with poor survival, whereas absence of VEGF-D/VEGFR-3 defined a subgroup of patients with clearly favorable prognosis. CONCLUSION: VEGF-D and VEGFR-3 are novel independent prognostic marker molecules aiding to identify patients with poor prognosis after curative resection of gastric adenocarcinomas. Combined analysis of the VEGF-C/VEGF-D/VEGFR-3 system can be useful to identify patients with unfavorable clinical outcome and thereby may help to refine therapeutic decisions in gastric cancer.
ISSN:0732-183X
Publisher:American Society of Clinical Oncology (U.S.A.)
Item Type:Article

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