Co-expression and prognostic significance of putative CSC markers CD44, CD133, wild-type EGFR and EGFRvIII in metastatic colorectal cancer

// Said Abdullah Khelwatty 1 , Sharadah Essapen 1, 2 , Izhar Bagwan 3 , Margaret Green 3 , Alan M. Seddon 1 and Helmout Modjtahedi 1 1 School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Kingston, UK 2 St. Luke’s Cancer Centre, Royal Surrey County Hospital, Guildford, Surrey, UK 3 Department of Histopathology, Royal Surrey County Hospital, Guildford, Surrey, UK Correspondence to: Helmout Modjtahedi, email: H.Modjtahedi@Kingston.ac.uk Keywords: CSC; colorectal cancer; EGFR; immunohistochemistry Received: January 15, 2019      Accepted: February 15, 2019      Published: March 01, 2019 ABSTRACT The presence of colorectal cancer stem cells (CSCs) have been associated with tumour initiation and resistance to therapy. This study investigated the co-expression and prognostic significance of the CSCs biomarkers CD44 and CD133 with wild-type EGFR (wtEGFR) and EGFRvIII in colorectal cancer (CRC). The expression of these biomarkers were determined in tumours from 70 patients with metastatic CRC by immunohistochemistry, and in a panel of human CRC cell lines, and their variants with acquired-resistance to EGFR inhibitors, by flow cytometry. The expression of CD44, CD133, wtEGFR and EGFRvIII were present in 17%, 23%, 26% and 13% of cases and the co-expression of CD44/CD133 with wtEGFR and EGFRvIII were present in 9% and 3% of the cases respectively. Only co-expression of CSCs/EGFRvIII ( P = 0.037), and amphiregulin ( P = 0.017) were associated with worse overall survival. Interestingly, disease-free survival was improved in BTC expressing patients ( P = 0.025). In vitro CD133 expression and its co-expression with CD44 were associated with primary-resistance to irinotecan and acquired-resistance to anti-EGFR inhibitors respectively. Our results suggest co-expression of CSCs and EGFRvIII could be potential biomarkers of worse overall survival and resistance to therapy in patients with mCRC and warrants further validation in a larger cohort.