The level of epidermal growth factor receptors expression is correlated with the advancement of colorectal adenoma: validation of a surface biomarker

Abstract

IntroductionData about the expression of Epidermal Growth Factor Receptors (EGFRs) in colorectal adenomas remain scarce.Results101 patients were enrolled including 53 controls. All adenomas (n = 38) and CRC (n = 5) were EGFR positive. Hyperplastic polyps (HP) (n = 8) and control colons (n = 53) were EGFR negative in half of cases (p < 0.0001). A well significant gradient of increased EGFR expression was observed between adjacent mucosa, hyperplastic lesions, low grade dysplasia (LGD) (n = 30), high grade dysplasia (HGD) adenomas (n = 9) and cancers (p < 0.0001). EGFR overexpression was reported in 100% of cancers, 77.8% of HGD, and 10% of LGD adenomas. By multivariate analysis in adenomas, associated factors with EGFR overexpression were HGD and tubulo-villous feature.Materials and MethodsAll patients undergoing colonoscopy in the university center of Saint-Etienne were eligible to the study from December 2015 to March 2016. In patients with colorectal neoplasia (lesions group), biopsies were performed on the lesion before its resection, and on the adjacent and distal colon mucosa. In control group, biopsies were performed in the right and left side colon. The EGFR expression was assessed by immunohistochemical scores (Goldstein grade, intensity of staining, composite score), using a primary mouse monoclonal antibody (EGFR, clone 113, Novocastra). Outcomes were compared using Kruskal-Wallis and/or Mann-Whitney-U tests, appropriately. The associated clinical, endoscopic and histological factors with EGFR overexpression (composite score ≥ 6) were assessed for adenomas by logistic regression.ConclusionsEGFR are early involved in colorectal carcinogenesis, and their expression is strongly correlated to the neoplasia stage, leading to validate EGFR as an interesting surface biomarker of adenomas.

A streamlined mass spectrometry–based proteomics workflow for large‐scale FFPE tissue analysis

“…Of interest, β-catenin (CTNNB1) and CDH1 showed the lowest expression differences between sections within the same and different patients, highlighting their homogeneous expression patterns in adenomas as previously reported [41,42]. Conversely, EGFR and CDX2 were variably expressed between adenomas within and between patients, again in-line with previous reports [43,44]. We further confirmed our proteomic results by immunohistochemistry (IHC) using validated antibodies (supplementary material, Figure S3).…”

A streamlined mass spectrometry-based proteomics workflow for large scale FFPE tissue analysis

“…Interestingly, ß-Catenin (CTNNB1) and CDH1 showed the lowest expression differences between sections within the same and different patients, highlighting their homogeneous expression patterns in adenomas as previously reported [37,38]. Conversely, EGFR and CDX2 were variably expressed between adenomas within and between patients, again in line with previous reports [39,40]. Together, these data demonstrate good workflow reproducibility and high proteome consistency within and across tissue sections of the same adenomas.…”

LGR5 expression is regulated by EGF in early colorectal adenomas and governs EGFR inhibitor sensitivity

“…This implies the contribution of additional factors to EGFRi sensitivity and this study suggests tumours with low LGR5 expression will exhibit increased sensitivity. Given that EGFR has recently been identified as a biomarker at the adenoma stage for more aggressive CRC progression ( Williet et al , 2017 ), our findings suggest that there could also be clinical benefit in assessing LGR5 expression at this early stage in order to stratify those patients who may respond best to EGFR therapy. LGR5 inhibitors have not been reported, but our data would suggest a combinatorial approach with EGFRi may synergise to reduce the survival of CRC cells.…”