Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. May 7, 2008; 14(17): 2691-2701
Published online May 7, 2008. doi: 10.3748/wjg.14.2691
Circulating lymphangiogenic growth factors in gastrointestinal solid tumors, could they be of any clinical significance?
Theodore D Tsirlis, George Papastratis, Kyriaki Masselou, Christos Tsigris, Antonis Papachristodoulou, Alkiviadis Kostakis, Nikolaos I Nikiteas
Theodore D Tsirlis, George Papastratis, Third Department of Surgery, General Hospital of Athens “G.Gennimatas”, Athens 115 26, Greece
Kyriaki Masselou, Department of Immunology, National Tissue Typing Center, General Hospital of Athens “G.Gennimatas”, Athens 115 26, Greece
Christos Tsigris, Antonis Papachristodoulou, Alkiviadis Kostakis, Nikolaos I Nikiteas, Second Department of Surgery, University of Athens Medical School, Laikon General Hospital, Athens 115 27, Greece
Author contributions: Tsirlis TD, Nikiteas NI contributed equally to conception and design of the review; Tsirlis TD wrote and revised the review; Papastratis G, Masselou K, Tsigris C, Papachristodoulou A and Kostakis A contributed equally to supportive work and supervision.
Correspondence to: Theodore D Tsirlis, Third Department of Surgery, General Hospital of Athens “G.Gennimatas”, Psaron 20 str. Agia Paraskevi, Athens 153 43, Greece.
Telephone: +30-210-6016351
Fax: +30-210-6867191
Received: January 8, 2008
Revised: March 22, 2008
Published online: May 7, 2008

Metastasis is the principal cause of cancer mortality, with the lymphatic system being the first route of tumor dissemination. The glycoproteins VEGF-C and VEGF-D are members of the vascular endothelial growth factor (VEGF) family, whose role has been recently recognized as lymphatic system regulators during embryogenesis and in pathological processes such as inflammation, lymphatic system disorders and malignant tumor metastasis. They are ligands for the VEGFR-3 receptor on the membrane of the lymphatic endothelial cell, resulting in dilatation of existing lymphatic vessels as well as in vegetation of new ones (lymphangiogenesis). Their determination is feasible in the circulating blood by immunoabsorption and in the tissue specimen by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Experimental and clinicopathological studies have linked the VEGF-C, VEGF-D/VEGFR3 axis to lymphatic spread as well as to the clinical outcome in several human solid tumors. The majority of these data are derived from surgical specimens and malignant cell series, rendering their clinical application questionable, due to subjectivity factors and post-treatment quantification. In an effort to overcome these drawbacks, an alternative method of immunodetection of the circulating levels of these molecules has been used in studies on gastric, esophageal and colorectal cancer. Their results denote that quantification of VEGF-C and VEGF-D in blood samples could serve as lymph node metastasis predictive biomarkers and contribute to preoperative staging of gastrointestinal malignancies.

Keywords: Circulating VEGF-C and VEGF-D, Gastric, Oesophageal, Colorectal cancer, Preoperative staging, Lymph node metastasis predictive markers