Original Article


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

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

Abstract

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.

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