title: Lymphangiogenesis and lymphovascular invasion diminishes prognosis in esophageal cancer.
abstract: BACKGROUND
  Tumor-associated lymphatic networks are the primary routes for tumor cell dissemination and metastasis. Behind the background of possible lymphangiogenesis-associated therapies, the clinical impact of lymphangiogenesis (measured by lymphatic microvessel density [LMVD]) and specific lymphovascular invasion (LVI) in esophageal cancer remains unclear. The aim of this study was to evaluate the clinical role of lymphangiogenesis and LVI in a large cohort of esophageal cancer.
  
  
  METHODS
  For the specific assessment of LMVD and LVI, 393 tissue samples from a prospective tissue databank of esophageal adenocarcinomas, squamous cell carcinomas, and their precursor lesions were included into this study. LMVD and LVI were assessed by immunostaining for podoplanin, a selective marker of lymphatic endothelium. In addition the peritumoral inflammatory stroma reaction (ISR) was assessed.
  
  
  RESULTS
  Patients with high LMVD had a significant increased risk to develop LVI (P = .00123; coefficient of regression [CR] 0.27) and lymph node metastasis (P = .00233), independent of the tumor's histology. During a follow-up of 52 months, patients with high LMVD had a significantly reduced overall survival (OS; P < .001; 5-year OS 30% vs 54%) and disease-free survival (DFS; P < .001; 5-year DFS 28% vs 48%). OS (P < .001; 5-year OS 14% vs 60%) and DFS (P < .001; 5-year DFS 14% vs 49%) were significantly reduced in patients with present LVI. In invasive cancer, LMVD was significantly increased compared with precursor lesions (P = .008). The amount of ISR correlated significantly with LMVD.
  
  
  CONCLUSIONS
  Our data provide evidence for a clinically significant role of specific lymphangiogenesis in esophageal cancer. Patients with high lymphangiogenic tumor activity represent candidates for lymphangiogenesis-associated therapies.
authors.affiliation: Department of Surgery, Upper GI Research Unit, Medical University of Vienna, Cancer Comprehensive Center Vienna GET, Vienna, Austria. sebastian.schoppmann@meduniwien.ac.at
authors.forename: Sebastian F
authors.initials: SF
authors.lastname: Schoppmann
authors.forename: Bettina
authors.initials: B
authors.lastname: Jesch
authors.forename: Johannes
authors.initials: J
authors.lastname: Zacherl
authors.forename: Martin F
authors.initials: MF
authors.lastname: Riegler
authors.forename: Julia
authors.initials: J
authors.lastname: Friedrich
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis; D000098853:Podoplanin
chemical_list: D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; C117468:PDPN protein, human; D000098853:Podoplanin