Table of Contents Author Guidelines Submit a Manuscript
Disease Markers
Volume 25, Issue 3, Pages 141-148
http://dx.doi.org/10.1155/2008/468323

Expression of Hypoxia-Inducible Factor (HIF)-1α and Vascular Endothelial Growth Factor (VEGF)-D As Outcome Predictors in Resected Esophageal Squamous Cell Carcinoma

Ching Tzao,1 Shih-Chun Lee,1 Ho-Jui Tung,3 Han-Shui Hsu,2 Wen-Hu Hsu,2 Guang-Huan Sun,4 Cheng-Ping Yu,5 Jong-Shiaw Jin,5 and Yeung-Leung Cheng1

1Division of Thoracic Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
2Division of Thoracic Surgery, Veterans General Hospital, Taipei, Taiwan
3Department of Humanity and Social Studies, National Defense Medical Center, Taipei, Taiwan
4Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
5Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

Received 5 December 2008; Accepted 5 December 2008

Copyright © 2008 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.