PWE-254 Is the macroscopically normal mucosa (MNM) around colorectal cancer really ‘normal’?

Field cancerisation refers to the process whereby cells acquire pro-tumourigenic mutations that predispose to malignant transformation but do not produce morphological change.1Previous colorectal cancer studies have assumed that the macroscopically normal mucosa (MNM) adjacent to a cancer is biologically unaltered. The aim of this study was to determine if the genetic expression profile of the MNM around a cancer or adenoma is different to that found in healthy controls. 15 patients undergoing colonoscopy were recruited over 12 months; 5 healthy controls, 5 with colorectal adenomas and 5 with adenocarcinoma. Two mucosal pinch biopsies were taken in the rectum, right colon and adjacent to polyp or cancer. mRNA was extracted and gene expression was assessed using standard whole genome micro-array analysis. Differentially expressed genes were identified using three methods of analysis: LIMMA (fold change ratio >1.5 and p value <0.05), Robust Regression (RR) (adjusted p value <0.05) and genes that ‘overlap’ when LIMMA (p value <0.001) and RR (adjusted p value <0.1) are used. Functional analysis was performed using DAVID2software to identify important biological processes that were dysregulated. A large number of genes were dysregulated in the MNM adjacent to cancer or adenoma compared with controls (Table 1). Interestingly, the greatest differences were seen between MNM adjacent to cancer and polyp in chromatin organisation, nucleosome processing, nuclear transport and histone assembly. The most significantly upregulated genes consisted of FUT2, CTSA, MUC2 and SDS and downregulated genes consisted of GREM1, SFRP, HIST1H, IL17B and TFF1.