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HIF-1α and VEGF are Associated with Disease Progression in Esophageal Carcinoma
- Source :
- Journal of Surgical Research. 167:41-48
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
Abstract
- Background Hypoxia inducible factor-1alpha (HIF-1α) is a transcription factor that regulates the transcription of genes associated with cell proliferation and angiogenesis. The purpose of this study is to clarify the correlation of HIF-1α protein expression with vascular endothelial growth factor (VEGF) and inducible (iNOS), endothelial (eNOS), and neuronal nitric oxide synthase (nNOS) expression in esophageal tumors. Additionally, vascular density in tumor tissue was assessed. Materials and Methods Eighty-eight esophageal carcinomas were analyzed by immunohistochemistry in paraffin embedded sections. Results HIF-1α immunoreactivity was seen in 71.2 % of the tumors. Squamous cell carcinomas expressed more often HIF-1α than adenocarcinomas (P = 0.009). HIF-1α immunoreactivity was associated with iNOS (P = 0.049), and iNOS positivity was also more commonly seen in squamous cell carcinomas than adenocarcinomas (P = 0.016). VEGF immunoreaction tended to associate with HIF-1α (P = 0.073) and iNOS (P = 0.08). ENOS did not associate with HIF-1α, but tended to associate with VEGF (P = 0.072). T1-T2 tumors were more often VEGF negative than T3-T4 tumors (P = 0.063). In the subgroup of 78 operatively treated ECs patients with HIF-1α positivity (>+) had more often distant metastases (P = 0.036). There was no association between iNOS, eNOS, nNOS, or VEGF, and microvessel density in tumor tissue, tumor marginal zone, or in peripheral tissue. Conclusions These results show that there is a link in expression between HIF-1α, iNOS, (eNOS), and VEGF in esophageal cancer. This is in line with the fact of HIF-1α's function as a transcriptional factor for these angiogenic factors. Results also show that squamous cell and adenocarcinomas differ in their expression of HIF-1α and iNOS. VEGF appear to have association with depth of invasion in esophageal carcinomas. In our material HIF-1α positivity was associated with distant metastases, but not with patient survival.
- Subjects :
- Vascular Endothelial Growth Factor A
Pathology
medicine.medical_specialty
Esophageal Neoplasms
Nitric Oxide Synthase Type III
Angiogenesis
Cell
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type I
Adenocarcinoma
Biology
Neovascularization
chemistry.chemical_compound
Enos
Biomarkers, Tumor
medicine
Carcinoma
Humans
Cell Proliferation
Retrospective Studies
Neovascularization, Pathologic
Esophageal cancer
Hypoxia-Inducible Factor 1, alpha Subunit
medicine.disease
biology.organism_classification
Vascular endothelial growth factor
medicine.anatomical_structure
chemistry
Case-Control Studies
Carcinoma, Squamous Cell
Disease Progression
Immunohistochemistry
Surgery
medicine.symptom
Subjects
Details
- ISSN :
- 00224804
- Volume :
- 167
- Database :
- OpenAIRE
- Journal :
- Journal of Surgical Research
- Accession number :
- edsair.doi.dedup.....a066dcddbc89a7f3015fac50ce1efc1b