PWE-001 field cancerisation theory in colorectal cancer (crc): what role do fibroblast growth factors have?

Characterisation of the molecular field defect around colorectal cancer (CRC) could enable identification of novel biomarkers that could be used for early detection of CRC. Previous studies have suggested fibroblast growth factor 19 (FGF19) may play a role in CRC formation through interaction with the B-catenin/wnt signalling cascade. The role of fibroblast growth factor 7 (FGF7) however remains controversial. The aim of this study was to determine if there are differences in FGF19 and FGF7 gene expression in cancer tissue and the adjacent ‘normal tissue’ compared with normal colonic tissue. Mucosal pinch biopsies were taken from the rectum and caecum at time of colonoscopy for healthy controls. For CRC patients, tissue samples were taken from the tumour, adjacent to the tumour and at the resection margin of the colectomy specimen. Healthy controls were age and sex matched to CRC patients. Quantitative real time PCR was used to determine gene expression of FGF19, its receptor FGFR4, FGF7 and its receptor, FGFR2. Results were further validated using immunohistochemistry. Serum levels of FGF19 were measured using the Quantikine ELISA kit (RandD systems, UK). 49 patients were recruited (28 M: 21 F, median age 71 years (range 48–86 years)); 18 patients with CRC and 32 healthy controls. There was no overall difference in gene expression of FGF19/FGFR4 or FGF7/FGFR2 between cancer patients and healthy controls. There was upregulation of FGFR4 in mucosa adjacent to the tumour (mean fold change 1.23 vs. 0.93, p = 0.38) and the tumour itself (mean fold change 1.49 vs. 1.04, p = 0.700) in patients whose tumour expressed FGF19 compared to those that did not. Patients with upregulation of FGF19/FGFR4 had a significantly lower fasting serum FGF19 level (119 pg/ml versus 208 pg/ml, p = 0.05). FGF7 was upregulated in 6/19 cancers; this was associated with a significant upregulation in FGF7 in adjacent mucosa compared with cancers where FGF7 was downregulated (mean fold change 3.62 vs. 0.95, p = 0.018). There was a non-significant trend towards upregulation of the receptor (FGFR2) in mucosa adjacent to the cancer and the tumour tissue itself. Upregulation of FGFR4 in patients whose tumours expressed FGF19 corresponded inversely with serum FGF19 suggesting its potential as a putative biomarker. Significant upregulation of FGF7 in ‘normal’ mucosa adjacent to only tumours that express FGF7 lends support to the field theory of colorectal carcinogenesis.