Article Abstract

Increased circulating levels of vascular endothelial growth factor C can predict outcome in resectable gastric cancer patients

Authors: Angelica Petrillo, Maria Maddalena Laterza, Giuseppe Tirino, Luca Pompella, Annalisa Pappalardo, Jole Ventriglia, Beatrice Savastano, Annamaria Auricchio, Michele Orditura, Fortunato Ciardiello, Gennaro Galizia, Ferdinando De Vita


Background: Neoangiogenesis has proven to be a relevant pathogenetic mechanism in gastric cancer (GC) and lymphatic spread represents an important well-known prognostic factor. Vascular endothelial growth factor C (VEGF-C) plays a key role in lymphangiogenesis and its blood levels in GC patients are easily measurable. This analysis aimed to investigate the prognostic role of preoperative VEGF-C blood levels.
Methods: VEGF-C serum levels were determined by enzyme-linked immunoadsorbent assay (ELISA) in 186 patients observed at our institution from January 2004 until December 2009 and 82 healthy subjects. Statistical analyses were performed using SPSS 21.0.
Results: VEGF-C levels were significantly higher in GC patients (median: 287.4 pg/mL; range, 76.2–865.2 pg/mL) than in the control group (median VEGF-C: 31 pg/mL; range, 12–97 pg/mL). A significant correlation between VEGF-C levels, T, N and tumor stage has been described. The median overall survival (OS) was statistically significantly higher in pts with low serum VEGF-C levels [median: not reached (NR) vs. 26 months; P<0.0001]. Higher preoperative VEGF-C levels correlated also with earlier disease relapse and poor disease-free survival (DFS) (median NR in each subgroup, P=0.005). Furthermore, high VEGF-C levels [hazard ratio (HR) =2.7; P=0.018] and tumor grading (HR =0.44; P=0.007) were independent prognostic factors for OS at multivariate analysis.
Conclusions: Our study showed that increased VEGF-C levels are significantly associated with advanced regional lymph node involvement and poor OS and DFS in pts with resected GC paving the way to a possible application as prognostic factor in the clinical practice.