Unit:
Τομέας Βασικών ΕπιστημώνLibrary of the School of Health Sciences
Author:
Ρηγόπουλος Δημήτριος
Dissertation committee:
Kαθ. Πατσούρης Ευστράτιος, Αν. Kαθ. Λάζαρης Ανδρέας, Αν. Kαθ. Καβαντζάς Νικόλαος
Original Title:
Διερεύνηση κριτηρίων συνδυασμένης αντί EGFR/VEGF στοχευμένης θεραπείας στο αδενοκαρκίνωμα του παχέος εντέρου σε ιστικές μικροσυστοιχίες
Summary:
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.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.
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.
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.
Keywords:
EGFR, VEGF, HIF-1a, Colon , Cancer
Number of references:
138
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