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Deregulation of EGFR/VEGF/HIF-1a signaling pathway in colon adenocarcinoma based on tissue microarrays analysis.
- Source :
-
Journal of B.U.ON. : official journal of the Balkan Union of Oncology [J BUON] 2010 Jan-Mar; Vol. 15 (1), pp. 107-15. - Publication Year :
- 2010
-
Abstract
- Purpose: Overexpression of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in colon adenocarcinoma (CA) is a frequent event, whereas specific deregulation mechanisms in the corresponding signaling pathways remain under investigation. Our aim was to co-evaluate their expression correlated to the hypoxia inducible factor 1alpha (HIF-1a), which activates the transcription of VEGF gene.<br />Methods: 60 paraffin-embedded primary CAs were cored at 1.5 mm diameter and transferred to the microarray block. Immunohistochemistry (IHC) was performed using anti-EGFR, -VEGF, and -HIF 1a monoclonal antibodies. Concerning EGFR, quantitative evaluation was based on a semi-automated analysis system. Chromogenic in situ hybridization (CISH) was performed using EGFR gene and chromosome 7 centromeric probes.<br />Results: Protein overexpression was observed in 13/60 (21.6%), 45/60 (75%) and 7/60 (11.6%) cases regarding EGFR, VEGF, and HIF 1a, respectively. CISH analysis detected 4/60 (6.6%) EGFR gene amplified cases, whereas chromosome 7 aneuploidy was identified in 11/60 (18.3%) cases. Significant associations raised correlating stage to chromosome 7 (p=0.024), HIF 1a expression to tumor anatomical location (p=0.019) and also VEGF to HIF 1a expression (p=0.001), whereas EGFR expression was not associated to EGFR gene copies.<br />Conclusion: According to our results, chromosome 7 instability is correlated to advanced disease, whereas a significant subset of CAs demonstrates an alternative, non- HIF 1a depended mechanism of VEGF overexpression. Furthermore, EGFR protein overexpression does not predict a specific gene deregulation mechanism.
- Subjects :
- Adenocarcinoma genetics
Adenocarcinoma pathology
Aged
Aged, 80 and over
Aneuploidy
Chromosomal Instability
Chromosomes, Human, Pair 7
Colonic Neoplasms genetics
Colonic Neoplasms pathology
ErbB Receptors genetics
Female
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
In Situ Hybridization
Male
Middle Aged
Neoplasm Staging
Paraffin Embedding
Adenocarcinoma chemistry
Colonic Neoplasms chemistry
ErbB Receptors analysis
Hypoxia-Inducible Factor 1, alpha Subunit analysis
Signal Transduction genetics
Tissue Array Analysis
Vascular Endothelial Growth Factor A analysis
Subjects
Details
- Language :
- English
- ISSN :
- 1107-0625
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of B.U.ON. : official journal of the Balkan Union of Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 20414936