Abstract
Objective
To evaluate the expression and correlation of hypoxia inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) and Survivin proteins in biopsy specimens of esophageal squamous cell carcinoma (ESCC), and then determine whether the levels of expression of these proteins could predict the clinical effectiveness of radiotherapy in individual cancers.
Methods
The expressions of HIF-1α, VEGF and Survivin were shown by S-P immunohistochemical staining method in biopsy specimens of ESCC, which were obtained endoscopically from 50 patients before radiotherapy, and 10 cases of normal esophageal tissue.
Results
The positive expression rates of HIF-1α, VEGF and Survivin were 68%, 74% and 72% in ESCC respectively. However, the three tumor markers had negative expressions in normal esophageal tissue. The positive rate of HIF-1α was positively correlated with VEGF and Survivin proteins. The positive rates of HIF-1α and Survivin were closely related to the clinical stage, radiotherapy effectiveness and survival, otherwise, the expression of HIF-1α was closely related to distant metastasis; both of them were no correlation with the differentiation degree of tumor. The effective rates of radiotherapy and mean survival periods of those cases with positive and negative expressions of HIF-1α were 8.8%, 10 months and 81.25%, 25 months, respectively. The one, two, and three years survival rates of patients with positive and negative expressions of HIF-1α were 38.2%, 5.9%, 2.9%, and 81.3%, 54.2%, 15.8%, respectively (P = 0.001). Patients with HIF-1α positive expression obviously survived less than those with negative expression and the difference was significant. The expression of VEGF was only related to the distant metastasis.
Conclusion
Over expressions of HIF-1α, VEGF and Survivin were found in ESCC. The positive rate of HIF-1α was positively correlated with VEGF and Survivin proteins. The expression of HIF-1α may serve as an important parameter in evaluating response for radiotherapy and prognosis of ESCC. It may play an important role by up-regulating the transcription of VEGF and Survivin genes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Tew WP, Kelsen DP, Ilson DH. Targeted therapies for esophageal cancer. Oncologist, 2005, 10: 590–601.
Yeo EJ, Chun YS, Park JW. New anticancer strategies targeting HIF-1. Biochem Pharmacol, 2004, 68: 1061–1069.
Zhu SC, Li R, Li J, et al. Preliminary study of clinical staging of mode lately advanced and advanced thoracic esophageal carcinoma. Clin J Radiat Oncol (Chinese), 2004, 13: 189–192.
Zhong H, De Marzo AM, Laughner E, et al. Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res, 1999, 59: 5830–5835.
Volm M, Koomagi R, Mattern J. Prognostic value of vascular endothelial growth factor and its receptor Flt-1 in squamous cell lung cancer. Int J Cancer, 1997, 74: 64–68.
Grabowski P, Kuhnel T, Muhr-Wilkenshoff F, et al. Prognostic value of nuclear survivin expression in oesophageal squamous cell carcinoma. Br J Cancer, 2003, 88: 115–119.
Kurokawa T, Miyamoto M, Kato K, et al. Overexpression of hypoxiainducible-factor 1alpha (HIF-1alpha) in oesophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage. Br J Cancer, 2003, 89: 1042–1047.
Sohda M, Ishikawa H, Masuda N, et al. Pretreatment evaluation of combined HIF-1alpha, p53 and p21 expression is a useful and sensitive indicator of response to radiation and chemotherapy in esophageal cancer. Int J Cancer, 2004, 110: 838–844.
Singhal S, Vachani A, Antin-Ozerkis D, et al. Prognostic implications of cell cycle, apoptosis, and angiogenesis biomarkers in non-small cell lung cancer: a review. Clin Cancer Res, 2005, 11: 3974–3986.
Rodel F, Hoffmann J, Distel L, et al. Survivin as a radioresistance factor, and prognostic and therapeutic target for radiotherapy in rectal cancer. Cancer Res, 2005, 65: 4881–4887.
Shih CH, Ozawa S, Ando N, et al. Vascular endothelial growth factor expression predicts outcome and lymph node metastasis in squamous cell carcinoma of the esophagus. Clin Cancer Res, 2000, 6: 1161–1168.
Du JR, Jiang Y, Zhang YM, et al. Vascular endothelial growth factoJin-Rong r and microvascular density in esophageal and gastric carcinomas. World J Gastroenterol, 2003, 9: 1604–1606.
Koshiji M, Kageyama Y, Pete EA, et al. HIF-1alpha induces cell cycle arrest by functionally counteracting Myc. EMBO J, 2004, 23: 1949–1956.
Yang L, Cao Z, Li F, et al. Tumor-specific gene expression using the survivin promoter is further increased by hypoxia. Gene Ther, 2004, 11: 1215–1223.
Matsuyama T, Nakanishi K, Hayashi T, et al. Expression of hypoxiainducible factor-1alpha in esophageal squamous cell carcinoma. Cancer Sci, 2005, 96: 176–182.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by a grant from the tackle key problems in science and technology of Hebei Province (No. 052761764).
Rights and permissions
About this article
Cite this article
Zhang, H., Wang, Y., Xu, N. et al. Expression and clinical significance of HIF-1α, VEGF and Survivin in esophageal squamous cell carcinoma. Chinese German J Clin Oncol 6, 339–344 (2007). https://doi.org/10.1007/s10330-007-0063-y
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10330-007-0063-y