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

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.

Regenerative proliferation of differentiated cells by mTORC 1‐dependent paligenosis

“…Chronically, however, ongoing damage and long-term metaplasia are associated with and may fuel the majority of gastric and pancreatic adenocarcinomas (Mills & Sansom, 2015;Giroux & Rustgi, 2017;Storz, 2017). In both organs, the cells of origin for the metaplastic, proliferating epithelial cells are thought to be differentiated secretory cells (zymogenic chief cells in the stomach and acinar cells in the pancreas) that reprogram to re-enter the cell cycle (Mills & Sansom, 2015;Murtaugh & Keefe, 2015;Radyk & Mills, 2017).…”

Histopathology of immature (ongoing) squamous metaplasia of the stomach

“…Universally, metaplasia is considered to be an adaptation response of the tissue and at the same time a precursor to dysplasia which can culminate in overt malignancy. Improved understanding of metaplasia is therefore considered to lead to better prevention or early detection of malignancies …”

“…In the stomach, metaplasia of the mucosa is frequently observed both endoscopically and histopathologically, and the overwhelming majority of metaplasia occurring in this organ is intestinal metaplasia (IM) in association with chronic gastritis . It is well known that gastric IM can progress to dysplasia and/or adenocarcinoma . By contrast, squamous metaplasia (SM) is the rarest form of metaplasia in the stomach, with only a few reported cases (Table S1).…”

“…Origin of these squamous precursor cells will be a subject of further study. Up until now, in any organs, the cell of origin for SM has not been clearly identified …”

Molecular evidence supporting the precursor nature of atypical adenomatous hyperplasia of the prostate

“…Telomere length abnormalities are nearly universal (97%) in the preinvasive stages of human epithelial carcinogenesis in all sites examined, and most of these abnormalities (89%) consist of telomere shortening . Telomere shortening is present in a wide variety of human epithelial cancer precursors, supporting the idea that telomere dysfunction plays a critical role in human carcinoma initiation …”