Expression of hypoxia-inducible factor (HIF)-1α
and vascular endothelial growth factor (VEGF)-D as outcome
predictors in resected esophageal squamous cell carcinoma
Affiliations: Division of Thoracic Surgery, Tri-Service General
Hospital, National Defense Medical Center, Taipei, Taiwan | Division of Thoracic Surgery, Veterans General
Hospital, Taipei, Taiwan | Department of Humanity and Social Studies, National
Defense Medical Center, Taipei, Taiwan | Department of Surgery, Tri-Service General Hospital,
National Defense Medical Center, Taipei, Taiwan | Department of Pathology, Tri-Service General Hospital,
National Defense Medical Center, Taipei, Taiwan
Note: [] Corresponding author: Ching Tzao, M.D., Ph.D., Division of
Thoracic Surgery, Tri-Service General Hospital, National Defense Medical
Center, 325, Section 2, Cheng Gong Road, Nei Hu, Taipei, Taiwan 114. Tel.: +886
2 87927167; Fax: +886 2 26347961; E-mail: [email protected]
Abstract: Hypoxia-inducible factor (HIF)-1α 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-1α expression remain elusive in esophageal
squamous cell cancer (ESCC). We studied expression of HIF-1α and VEGF-D
using immunohistochemistry in 85 resected ESCC specimens and correlated results
with patients' clinicopathologic parameters and survival. Association between
expression of HIF-1α and VEGF-D was investigated using a concordance
analysis. High expression of HIF-1α and VEGF-D was observed in 52
(61.2%) and 56 (65.9%) patients, respectively. HIF-1α 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-1α and VEGF-D showed worse survivals than those of low
expression (P = 0.002 and 0.001, respectively). Multivariate analysis
supported expression of HIF-1α 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-1α and VEGF-D. In conclusion,
protein expression of HIF-1α and VEGF-D are independent prognostic
predictors. An association between expression of HIF-1α and VEGF-D
suggests that these two angiogenic factors are essential in progression of
ESCC.
