title: Prognostic significance of targetable angiogenic and growth factors in patients undergoing resection for gastric and gastroesophageal junction cancers.
abstract: BACKGROUND
  Circulating factors in patients with gastric/gastroesophageal junction (GEJ) cancers may promote tumor progression and metastasis and may be targeted for therapy.
  
  
  METHODS
  Serum levels of ligands-vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF2), epidermal growth factor (EGF), hepatocyte growth factor (HGF)-from four targetable pathways were measured before surgery, and levels were correlated to clinicopathologic characteristics and overall survival (OS).
  
  
  RESULTS
  In 147 patients who underwent potentially curative resection for gastric/GEJ adenocarcinoma, VEGF-A levels were higher in patients with R1 versus R0 resection (p = 0.037). High EGF levels were associated with poorly differentiated tumors (p = 0.02). Elevated FGF2 levels were found in Lauren diffuse-type tumors (p = 0.017) and tumors with seven or more metastatic nodes (N3) (p < 0.042). Patients with advanced-staged tumors had higher HGF levels (p = 0.012). At a median follow-up of 35 months, 46 patients (31 %) had died. Increased VEGF and HGF levels were correlated with decreased OS (p = 0.009 and 0.005). An adjusted total value (ATV) of all factors was better than any single factor in stratifying patients into good and poor prognosis groups (5-year OS 84.1 vs. 53.9 %, p = 0.005). By multivariate analysis, serum VEGF-A and ATV were significant independent prognostic factors (along with T and N category) for OS (p = 0.028 and 0.013, respectively).
  
  
  CONCLUSIONS
  In patients undergoing resection for gastric and GEJ cancer, high levels of angiogenic and growth factors are associated with unfavorable tumor characteristics and poorer overall survival. Thus levels of these factors can help delineate tumor biology and stratify prognosis.
authors.affiliation: Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Do Joong
authors.initials: DJ
authors.lastname: Park
authors.forename: Changhwan
authors.initials: C
authors.lastname: Yoon
authors.forename: Nicholas
authors.initials: N
authors.lastname: Thomas
authors.forename: Geoffrey Y
authors.initials: GY
authors.lastname: Ku
authors.forename: Yelena Y
authors.initials: YY
authors.lastname: Janjigian
authors.forename: David P
authors.initials: DP
authors.lastname: Kelsen
authors.forename: David H
authors.initials: DH
authors.lastname: Ilson
authors.forename: Karyn A
authors.initials: KA
authors.lastname: Goodman
authors.forename: Laura H
authors.initials: LH
authors.lastname: Tang
authors.forename: Vivian E
authors.initials: VE
authors.lastname: Strong
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Coit
authors.forename: Sam S
authors.initials: SS
authors.lastname: Yoon
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D004815:Epidermal Growth Factor / Q000097:blood*; D004938:Esophageal Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D004943:Esophagogastric Junction / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood*; D005500:Follow-Up Studies; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor