Metaplasia: tissue injury adaptation and a precursor to the dysplasia–cancer sequence

Abstract

Metaplasia is the replacement of one differentiated cell type with another mature differentiated cell type that is not normally present in that tissue. Metaplasia, when persistent, can be a precursor to dysplasia, which can in turn progress to carcinoma. As a result, recognition of metaplasia through screening and surveillance modalities is important and could reveal potential strategies for both cancer prevention and therapy. Metaplasia is an adaptive response to injurious agents, which are largely environmental in nature (for example, acid, bile, cigarette smoke and alcohol), but is also influenced by the actions of microorganisms (for example, Helicobacter pylori and human papillomavirus (HPV)). Different types of metaplasia exist, depending upon the tissue source: squamous, intestinal and acinar–ductal. The cell of origin has been postulated to be from the gastric cardia in oesophageal intestinal metaplasia and to be triggered by loss of parietal cells in gastric intestinal metaplasia. Metaplastic cell-autonomous (for example, mutant KRAS signalling) and non-cell-autonomous mechanisms contribute to the development and maintenance of metaplasia.