Marinović, Sonja; Vuković, Kristina; Škrtić, Anita; Poljak, Mirko; Petek, Sara; Petek, Lara; Kapitanović, Sanja
(2020)
Epidermal growth factor receptor intron 1 polymorphism and microsatellite instability in sporadic colorectal cancer.
Oncology Letters, 21
(2).
ISSN 1792-1074
Abstract
Epidermal growth factor receptor (EGFR) expression is commonly upregulated in sporadic colorectal cancer (CRC) and its high expression is associated with poor prognosis in patients with CRC. CA‑SSR1 is a dinucleotide CA repeat of the EGFR gene that can modulate EGFR transcription and is a potential target of the mismatch repair machinery in tumours with microsatellite instability (MSI). In the present study, 160 sporadic colon cancer samples were analysed for EGFR CA‑SSR1 polymorphism and MSI status. Additionally, EGFR mRNA and protein expression levels in the tumour centre and in the invasive tumour front, compared with those in adjacent normal tissue samples, were evaluated in 80 tumour samples. An inverse association was identified between EGFR mRNA levels and the sum of repeats in both alleles of the CA‑SSR1 polymorphism in normal tissues. Changes in CA‑SSR1 were detected in the tumour centre as well as in the invasive tumour front and metastases in all MSI high (MSI‑H) tumours. Analysis of EGFR expression at the mRNA and protein levels according to MSI status revealed lower EGFR mRNA and protein expression in MSI‑H tumours than microsatellite‑stable (MSS) tumours. Furthermore, higher EGFR levels in the invasive tumour front compared with in the tumour centre in MSS tumours were identified, suggesting a role of EGFR in tumour progression and higher invasive potential of MSS than MSI‑H tumours.
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