Deregulation of EGFR/VEGF/HIF-1a signaling pathway in colon adenocarcinoma based on tissue microarrays analysis

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are frequently overexpressed in colon adenocarcinoma (CA).
• The specific deregulation mechanisms underlying EGFR and VEGF overexpression in CA signaling pathways require further investigation.
• Hypoxia-inducible factor 1-alpha (HIF-1a) is known to activate the transcription of the VEGF gene.

Purpose of the Study:

• To co-evaluate the expression of EGFR and VEGF in colon adenocarcinoma.
• To correlate EGFR and VEGF expression with hypoxia-inducible factor 1-alpha (HIF-1a) expression.
• To investigate the underlying gene deregulation mechanisms for EGFR and VEGF.

Main Methods:

• Analysis of 60 paraffin-embedded primary colon adenocarcinoma (CA) samples using tissue microarrays.
• Immunohistochemistry (IHC) to assess protein expression of EGFR, VEGF, and HIF-1a.
• Quantitative evaluation of EGFR protein expression via semi-automated analysis and assessment of EGFR gene amplification and chromosome 7 copy number using chromogenic in situ hybridization (CISH).

Main Results:

• Protein overexpression rates were: EGFR (21.6%), VEGF (75%), and HIF-1a (11.6%).
• EGFR gene amplification was detected in 6.6% of cases, and chromosome 7 aneuploidy in 18.3%.
• Significant correlations were found between tumor stage and chromosome 7 (p=0.024), HIF-1a expression and tumor location (p=0.019), and VEGF and HIF-1a expression (p=0.001). EGFR expression was not associated with EGFR gene copy number.

Conclusions:

• Chromosome 7 instability is associated with advanced colon adenocarcinoma disease.
• A subset of colon adenocarcinomas exhibits VEGF overexpression through mechanisms independent of HIF-1a.
• EGFR protein overexpression does not appear to be linked to a specific EGFR gene deregulation mechanism in this cohort.