Abhilasha Patel1,2, Gyanendra Tripathi2, Philip McTernan2, Kishore Gopalakrishnan3, Omar Ali2, Emma Spector2, Nigel Williams1, Ramesh P Arasaradnam2,4,5,6. 1. Department of Colorectal Surgery, University Hospitals of Coventry and Warwickshire NHS Trust, Coventry, UK. 2. Warwick Medical School, University of Warwick, Coventry, UK. 3. Department of Pathology, University Hospitals of Coventry and Warwickshire NHS Trust, Coventry, UK. 4. Department of Gastroenterology, University Hospitals of Coventry and Warwickshire NHS Trust, Coventry, UK. 5. University of Coventry, Coventry, UK. 6. University of Leicester, Leicester, UK.
Abstract
BACKGROUND: Field cancerisation proposes that there are pre-malignant genetic mutations in the macroscopically normal mucosal tissue around colorectal cancer. This study aims to evaluate fibroblast growth factor 7 (FGF7) tissue expression in the mucosal field around colorectal cancer. METHODS: Gene and protein expression of FGF7, its receptor, FGFR2 and its downstream targets; FRS2α, Erk 1/2 and Akt was measured from mucosal samples in 34 control subjects and 17 cancer patients. Serial samples from tumour, adjacent to tumour and at the resection margin were utilised. RESULTS: FGF7 gene expression was significantly higher in tumour (2.3-fold), adjacent mucosa (3.2-fold) and resection margin (2.8-fold) of cancer patients compared with control subjects (P<0.01 respectively). However, FGFR2 was down regulated (3.5-fold) in the tumour tissue (P<0.001). Protein expression of FRS2α and Akt was significantly lower in tumour tissue compared with the resection margin in cancer patients (P<0.05 respectively). No differences in protein expression of Erk 1/2 were detected. CONCLUSIONS: FGF7 was elevated in the mucosal field of cancer patients supporting its potential as a biomarker of field cancerisation. Changes in FRS2α, Akt and Erk 1/2 expression in the tumour tissue indicate that with malignant transformation, FGF7 loses its ability to regulate cellular differentiation.
BACKGROUND: Field cancerisation proposes that there are pre-malignant genetic mutations in the macroscopically normal mucosal tissue around colorectal cancer. This study aims to evaluate fibroblast growth factor 7 (FGF7) tissue expression in the mucosal field around colorectal cancer. METHODS: Gene and protein expression of FGF7, its receptor, FGFR2 and its downstream targets; FRS2α, Erk 1/2 and Akt was measured from mucosal samples in 34 control subjects and 17 cancer patients. Serial samples from tumour, adjacent to tumour and at the resection margin were utilised. RESULTS: FGF7 gene expression was significantly higher in tumour (2.3-fold), adjacent mucosa (3.2-fold) and resection margin (2.8-fold) of cancer patients compared with control subjects (P<0.01 respectively). However, FGFR2 was down regulated (3.5-fold) in the tumour tissue (P<0.001). Protein expression of FRS2α and Akt was significantly lower in tumour tissue compared with the resection margin in cancer patients (P<0.05 respectively). No differences in protein expression of Erk 1/2 were detected. CONCLUSIONS: FGF7 was elevated in the mucosal field of cancer patients supporting its potential as a biomarker of field cancerisation. Changes in FRS2α, Akt and Erk 1/2 expression in the tumour tissue indicate that with malignant transformation, FGF7 loses its ability to regulate cellular differentiation.
Entities:
Keywords:
Fibroblast growth factor; colorectal cancer; field cancerisation
Authors: Thomas Amann; Frauke Bataille; Thilo Spruss; Katja Dettmer; Peter Wild; Christian Liedtke; Marcus Mühlbauer; Paul Kiefer; Peter J Oefner; Christian Trautwein; Anja-Katrin Bosserhoff; Claus Hellerbrand Journal: Am J Pathol Date: 2010-01-21 Impact factor: 4.307
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