Published online Apr 7, 2015. doi: 10.3748/wjg.v21.i13.3763
Peer-review started: November 28, 2014
First decision: December 26, 2014
Revised: January 9, 2015
Accepted: February 12, 2015
Article in press: February 13, 2015
Published online: April 7, 2015
Despite considerable advances in our understanding of cancer biology, early diagnosis of colorectal cancer remains elusive. Based on the adenoma-carcinoma sequence, cancer develops through the progressive accumulation of mutations in key genes that regulate cell growth. However, recent mathematical modelling suggests that some of these genetic events occur prior to the development of any discernible histological abnormality. Cells acquire pro-tumourigenic mutations that are not able to produce morphological change but predispose to cancer formation. These cells can grow to form large patches of mucosa from which a cancer arises. This process has been termed “field cancerisation”. It has received little attention in the scientific literature until recently. Several studies have now demonstrated cellular, genetic and epigenetic alterations in the macroscopically normal mucosa of colorectal cancer patients. In some reports, these changes were effectively utilised to identify patients with a neoplastic lesion suggesting potential application in the clinical setting. In this article, we present the scientific evidence to support field cancerisation in colorectal cancer and discuss important limitations that require further investigation. Characterisation of the field defect is necessary to enable early diagnosis of colorectal cancer and identify molecular targets for chemoprevention. Field cancerisation offers a promising prospect for experimental cancer research and has potential to improve patient outcomes in the clinical setting.
Core tip: There is a great deal of interest in developing non- invasive tests that are able to detect colorectal cancer in the asymptomatic population. Most current research activity is focussed on investigating the biological changes found in tumour tissue itself. This review evaluates the biological alterations found in the normal mucosa around a neoplastic lesion and critically analyses the concept of field cancerisation. It highlights recent advances and identifies important molecular targets that could play a role in early colorectal carcinogenesis. In particular, the available evidence for field cancerisation is scrutinised and future avenues for further scientific enquiry are outlined.