title: Coexpression of the IGF-IR, EGFR and HER-2 is common in colorectal cancer patients.
abstract: Signalling via the insulin-like growth factor-I receptor (IGF-IR) has been associated with resistance to anti-epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 (HER-2)-based therapies in the experimental system, but the coexpression and clinical significance of the IGF-IR, EGFR and HER-2 in cancer patients remains unclear. IGF-IR, EGFR, and HER-2 status was assessed retrospectively in tumour specimens from 87 Dukes' C colorectal cancer patients using immunohistochemistry. Sections were scored by the percentage of positive cells (membrane and cytoplasmic) and intensity of staining. The association between receptor coexpression and clinicopathological parameters and overall survival were evaluated using univariate and multivariate (Cox) analysis. Overall, 93, 83 and 89% of the cases expressed IGF-IR, EGFR and HER-2, respectively. While 60% of the cases expressed membranous IGF-IR, the expression of EGFR and HER-2 was predominantly cytoplasmic. Coexpression of the IGF-IR, EGFR and HER-2 was present in tumours from 75% of the patients. No significant association was found between the expression or coexpression of total IGF-IR, EGFR and HER-2 and clinicopathological parameters or overall survival. Our results indicate that coexpression of IGF-IR, EGFR and HER-2 is common in Dukes' C colorectal cancer, warranting further investigation on the co-targeting of such receptors in colorectal cancer patients.
authors.affiliation: Division of Oncology, Postgraduate Medical School, Guildford, Surrey GU2 7WG, UK.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Cunningham
authors.forename: Sharadah
authors.initials: S
authors.lastname: Essapen
authors.forename: Hilary
authors.initials: H
authors.lastname: Thomas
authors.forename: Margaret
authors.initials: M
authors.lastname: Green
authors.forename: David P
authors.initials: DP
authors.lastname: Lovell
authors.forename: Clare
authors.initials: C
authors.lastname: Topham
authors.forename: Christopher
authors.initials: C
authors.lastname: Marks
authors.forename: Helmout
authors.initials: H
authors.lastname: Modjtahedi
mesh_terms: D000368:Aged; D002462:Cell Membrane / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D017526:Receptor, IGF Type 1