title: Expression of hypoxia-inducible factor (HIF)-1alpha and vascular endothelial growth factor (VEGF)-D as outcome predictors in resected esophageal squamous cell carcinoma.
abstract: Hypoxia-inducible factor (HIF)-1alpha and vascular endothelial growth factor (VEGF) are important angiogenic factors in human cancers. Relative to VEGF-C, prognostic significance of VEGF-D expression and its association with HIF-1alpha expression remain elusive in esophageal squamous cell cancer (ESCC). We studied expression of HIF-1alpha and VEGF-D using immunohistochemistry in 85 resected ESCC specimens and correlated results with patients' clinicopathologic parameters and survival. Association between expression of HIF-1alpha and VEGF-D was investigated using a concordance analysis. High expression of HIF-1alpha and VEGF-D was observed in 52 (61.2%) and 56 (65.9%) patients, respectively. HIF-1alpha expression correlated well with tumor stage (P = 0.041), whereas VEGF-D expression correlated with tumor stage (P = 0.027) and N status (P = 0.019). Groups of high HIF-1alpha and VEGF-D showed worse survivals than those of low expression (P = 0.002 and 0.001, respectively). Multivariate analysis supported expression of HIF-1alpha and VEGF-D as significant survival predictors (P = 0.044 and 0.035, respectively). A concordance rate of 69.5% was observed between expression of HIF-1alpha and VEGF-D. In conclusion, protein expression of HIF-1alpha and VEGF-D are independent prognostic predictors. An association between expression of HIF-1alpha and VEGF-D suggests that these two angiogenic factors are essential in progression of ESCC.
authors.affiliation: Division of Thoracic Surgery, Tri-Service General Hospital, National Defense Medical Center, Nei Hu, Taipei, Taiwan. tzao@yahoo.com
authors.forename: Ching
authors.initials: C
authors.lastname: Tzao
authors.forename: Shih-Chun
authors.initials: SC
authors.lastname: Lee
authors.forename: Ho-Jui
authors.initials: HJ
authors.lastname: Tung
authors.forename: Han-Shui
authors.initials: HS
authors.lastname: Hsu
authors.forename: Wen-Hu
authors.initials: WH
authors.lastname: Hsu
authors.forename: Guang-Huan
authors.initials: GH
authors.lastname: Sun
authors.forename: Cheng-Ping
authors.initials: CP
authors.lastname: Yu
authors.forename: Jong-Shiaw
authors.initials: JS
authors.lastname: Jin
authors.forename: Yeung-Leung
authors.initials: YL
authors.lastname: Cheng
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000556:secondary / Q000601:surgery; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D009367:Neoplasm Staging; D016896:Treatment Outcome; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042643:Vascular Endothelial Growth Factor D