title: Vascular endothelial growth factor C and D expression correlates with lymph node metastasis and poor prognosis in patients with resected esophageal cancer.
abstract: Vascular endothelial growth factors C (VEGF-C) and D (VEGF-D) are important lymphangiogenic factors in human cancers. We studied the expression of VEGF-C and VEGF-D using immunohistochemistry in 73 resected esophageal cancer specimens, and correlated the results with patient clinicopathologic features and survival. High expression of VEGF-C was identified in 40 (54.7%) patients, and it correlated positively with histological grade (p=0.038), tumor stage (p=0.01), depth of tumor invasion (p=0.036) and lymph node metastasis (p=0.001). In 48 of 73 (65.7%) tumors, the VEGF-D protein was also expressed at high levels. VEGF-D immunoreactivity significantly correlated with tumor location (p=0.027), size of tumor (p=0.015), histological grade (p=0.02), depth of invasion (p=0.001) and lymph node metastasis (p=0.018). In logistic multivariate analysis, high expression of VEGF-C (OR 1.941, 95% CI 1.263-7.289, p=0.024) was associated with lymph node metastasis. Calculating the prognostic relevance revealed that both VEGF-C and VEGF-D correlated with decreased overall survival (p=0.01, p=0.003), disease free survival (p=0.02, p=0.006), and cancer-specific survival (p=0.03, p=0.005). In conclusion, our results suggest that high levels of both VEGF-C and VEGF-D proteins are associated with lymph node involvement, and that VEGF-C expression is an independent predictor of risk for lymph node metastasis in esophageal cancer. In locally advanced disease, overexpression of VEGF-C and VEGF-D may be useful in identifying patients who are more likely to have a poor prognosis even after curative resection.
authors.affiliation: Department of Thoracic Surgery, Medical University of Biolystok, 24A Sklodowskiej-Curie Str, Bialystok, Poland. miroslaw@cksr.ac.bialystok.pl
authors.forename: M
authors.initials: M
authors.lastname: Kozlowski
authors.forename: W
authors.initials: W
authors.lastname: Naumnik
authors.forename: J
authors.initials: J
authors.lastname: Niklinski
authors.forename: R
authors.initials: R
authors.lastname: Milewski
authors.forename: P
authors.initials: P
authors.lastname: Dziegielewski
authors.forename: J
authors.initials: J
authors.lastname: Laudanski
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis*; D042643:Vascular Endothelial Growth Factor D / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D