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

Key Points

  • 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.

Abstract

Metaplasia is the replacement of one differentiated somatic cell type with another differentiated somatic cell type in the same tissue. Typically, metaplasia is triggered by environmental stimuli, which may act in concert with the deleterious effects of microorganisms and inflammation. The cell of origin for intestinal metaplasia in the oesophagus and stomach and for pancreatic acinar–ductal metaplasia has been posited through genetic mouse models and lineage tracing but has not been identified in other types of metaplasia, such as squamous metaplasia. A hallmark of metaplasia is a change in cellular identity, and this process can be regulated by transcription factors that initiate and/or maintain cellular identity, perhaps in concert with epigenetic reprogramming. Universally, metaplasia is a precursor to low-grade dysplasia, which can culminate in high-grade dysplasia and carcinoma. Improved clinical screening for and surveillance of metaplasia might lead to better prevention or early detection of dysplasia and cancer.

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Figure 1: Squamous metaplasia.
Figure 2: Intestinal metaplasia in the oesophagus.
Figure 3: Acinar–ductal metaplasia.
Figure 4: Spasmolytic polypeptide-expressing metaplasia and gastric intestinal metaplasia.

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Acknowledgements

This work was funded in part through the National Cancer Institute and the American Cancer Society. The authors apologize in advance if all relevant references were not able to be cited.

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A.K.R. and V.G. researched the data for the article, wrote the article and reviewed and/or edited the manuscript before its submission. A.K.R. made substantial contributions to the discussions of the content.

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Correspondence to Anil K. Rustgi.

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Glossary

Dysplasia

A condition in which cells have abnormal cellular architecture, with nuclear atypia, nuclear hyperchromasia and loss of cell polarity.

Glandular stomach

The part of stomach that is responsible for normal physiological functions.

Parietal cells

Also known as oxyntic cells, these are the acid-producing cells in the stomach epithelium.

Chief cells

Pepsinogen- and chymosin-producing cells in the stomach epithelium.

Atrophic gastritis

Loss of segments of the gastric mucosa in the setting of inflammation.

Spasmolytic polypeptide-expressing metaplasia

(SPEM). Metaplastic cells that are marked by spasmolytic polypeptide expression in the stomach epithelium.

Brush border

The small intestinal epithelial microvilli-covered surface that expresses brush border enzymes that mediate the transport of micronutrients from the lumen to within the epithelium.

Exocrine pancreas

Compartments of acinar and ductal cells that secrete and transport digestive enzymes.

Gastric cardia

The small region that constitutes the first part of the stomach and is composed of columnar cells.

Oesophageal submucosal glands

Distinct structures below the oesophageal epithelium that have secretory functions.

Foveolar hyperplasia

A characteristic of reactive gastritis observed in the gastric antrum and body.

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Giroux, V., Rustgi, A. Metaplasia: tissue injury adaptation and a precursor to the dysplasia–cancer sequence. Nat Rev Cancer 17, 594–604 (2017). https://doi.org/10.1038/nrc.2017.68

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