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James R. Goldenring - One of the best experts on this subject based on the ideXlab platform.
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Pyloric Metaplasia, pseudopyloric Metaplasia, ulcer-associated cell lineage and spasmolytic polypeptide-expressing Metaplasia: reparative lineages in the gastrointestinal mucosa.
The Journal of Pathology, 2018Co-Authors: James R. GoldenringAbstract:: The gastrointestinal mucosae provide a critical barrier between the external and internal milieu. Thus, damage to the mucosa requires an immediate response to provide appropriate wound closure and healing. Metaplastic lineages with phenotypes similar to the mucous glands of the distal stomach or Brunner's glands have been associated with various injurious scenarios in the stomach, small bowel, and colon. These lineages have been assigned various names including pyloric Metaplasia, pseudopyloric Metaplasia, ulcer-associated cell lineage (UACL), and spasmolytic polypeptide-expressing Metaplasia (SPEM). A re-examination of the literature on these various forms of mucous cell Metaplasia suggests that pyloric-type mucosal gland lineages may provide a ubiquitous response to mucosal injury throughout the gastrointestinal tract as well as in the pancreas, esophagus, and other mucosal surfaces. While the cellular origin of these putative reparative lineages likely varies in different regions of the gut, their final phenotypes may converge on a pyloric-type gland dedicated to mucous secretion. In addition to their healing properties in the setting of acute injury, these pyloric-type lineages may also represent precursors to neoplastic transitions in the face of chronic inflammatory influences. Further investigations are needed to determine how discrete molecular profiles relate to the origin and function of pyloric-type Metaplasias previously described by histological characteristics in multiple epithelial mucosal systems in the setting of acute and chronic damage. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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gene expression profiling of metaplastic lineages identifies cdh17 as a prognostic marker in early stage gastric cancer
Gastroenterology, 2010Co-Authors: Heae Surng Park, Bonnie Lafleur, Hiroyuki Aburatani, Hankwang Yang, James R. GoldenringAbstract:BACKGROUND & AIMS: Intestinal Metaplasia (IM) and spasmolytic polypeptide-expressing Metaplasia (SPEM) are precursors to gastric carcinogenesis. We sought to identify molecular biomarkers of gastric Metaplasias and gastric cancer by gene expression profiling of metaplastic lesions from patients. METHODS: Complementary DNA microarray analysis was performed on IM and SPEM cells isolated from patient samples using laser capture microdissection. Up-regulated transcripts in metaplastic lesions were confirmed by immunostaining analysis in IM, SPEM, and gastric cancer tissues. Proteins that were highly expressed specifically in gastric cancer tissues were analyzed for their association with survival in a test set (n = 450) and a validation set (n = 502) of samples from gastric cancer patients. RESULTS: Compared with normal chief cells, 858 genes were differentially expressed in IM or SPEM samples. Immunostaining was detected for 12 proteins, including 3 new markers of IM (ACE2, LGALS4, AKR1B10) and 3 of SPEM (OLFM4, LYZ, DPCR1). Of 13 proteins expressed in IM or SPEM, 8 were expressed by 17%-50% of human gastric cancer tissues (MUC13, OLFM4, CDH17, KRT20, MUC5AC, LGALS4, AKR1B10, REG4). Expression of CDH17 or MUC13 correlated with patient survival in the test and validation sets. Multivariate analysis showed that CDH17 was an independent prognostic factor in patients with stage I or node-negative disease. CONCLUSIONS: We identified several novel biomarkers for IM, SPEM, and gastric cancer using gene expression profiling of human metaplastic lesions. Expression of CDH17 and MUC13 was up-regulated in gastric cancer tissues. CDH17 is a promising prognostic marker for early stage gastric cancer.
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Spasmolytic Polypeptide-Expressing Metaplasia and Intestinal Metaplasia: Time for Reevaluation of Metaplasias and the Origins of Gastric Cancer
Gastroenterology, 2010Co-Authors: James R. Goldenring, Ki Taek Nam, Timothy C. Wang, Jason C. Mills, Nicholas A. WrightAbstract:Gastric adenocarcinoma of the intestinal type is believed to develop through a series of histopathologic stages, originally described by Correa, that include chronic gastritis, gastric atrophy, intestinal Metaplasia, dysplasia and finally cancer (1). Intestinal Metaplasia has been the focus of great fascination by many pathologists, since it was unexpected to find intestinal type mucosa containing goblet cells in the body or antrum of the stomach. Numerous studies have implicated intestinal Metaplasia as a useful biomarker for gastric cancer risk, and even possibly a precursor to gastric malignancy. However, this evidence has been largely correlative. In patients with gastric cancer, intestinal Metaplasia is frequently found in the stomach, even with early gastric cancer. Intestinal Metaplasia is much more prevalent in high-risk areas for gastric cancer compared to low risk areas. Finally, in several studies where serial endoscopies and biopsies were performed, patients with intestinal Metaplasia, particularly type III, frequently developed gastric cancer (2). Intestinal Metaplasia has been used as the key biomarker in studies of H. pylori eradication or gastric cancer prevention, defining the preneoplastic lesion often considered the “point-of-no-return” (3). Indeed, since the gastric cancers that developed in this setting also showed intestinal differentiation, it seemed logical to conclude that the cancers arose directly from these intestinal metaplastic cells. Neverthless, in contrast with other neoplasms, little genetic mutational evidence exists to implicate intestinal metaplastic lineages as true direct precursors of gastric neoplasia. Recent investigations have also highlighted the existence of a second metaplastic lineage, Spasmolytic Polypeptide-Expressing Metaplasia (SPEM) (4). SPEM is a metaplastic mucous cell lineage with phenotypic characteristics of deep antral gland cells including strong expression of Trefoil Factor 2 (TFF2, previously designated as spasmolytic polypeptide). In the past, this underappreciated mucous lineage was described with various names including pseudopyloric Metaplasia or mucous Metaplasia or antralization of the corpus, but mostly the lineage was ignored. Indeed, it is now appreciated that atrophy of the corpus and body of the stomach is always associated with the development of SPEM. In addition, SPEM is at least as strongly associated with the development of gastric cancer as intestinal Metaplasia (4). Moreover, while intestinal Metaplasia tends to be spotty or multifocal, SPEM typically appears diffusely throughout the body and corpus of the stomach in patients that progress to gastric cancer (5). SPEM is not simply an expansion of antral type mucosa, since gastrin cells are not present and SPEM cells express a number of proteins, such as HE-4, that are not expressed in the antrum (6). However, both the precise connection between intestinal Metaplasia and SPEM and the relationship between SPEM and gastric cancer remain unclear. Recent studies have examined the cellular origin of SPEM in mice. These investigations have demonstrated that SPEM develops in the fundus in the setting of parietal cell loss following chronic Helicobacter infection (7, 8). acute parietal cell loss due to treatment with DMP-777 (9), or chronic genetic parietal cell ablation by transgenically expressed toxin (10). These studies have led to accumulating evidence that SPEM may originate from transdifferentiation of mature chief cells into SPEM (6). In the case of H. felis infection, gastritis cystica profunda and dysplasia evolve from preexisting regions of SPEM (11). Still these studies have not been able to address intestinal Metaplasia because Helicobacter-infected mice do not typically develop intestinal Metaplasia. Intestinal goblet cells do develop in the fundus of transgenic mice where cdx2, a transcription factor, which is a master developmental regulator of intestinal differentiation, is targeted to the stomach using elements of the H+/K+-ATPase β subunit promoter (12, 13). Interestingly, amphiregulin-deficient mice developed SPEM after 6 months of age, and a subset of mice did go on to develop goblet cell intestinal Metaplasia (14). In that case, compound glands containing both SPEM and intestinal Metaplasia were clearly present. While murine studies have not been able to clarify the relationship between intestinal Metaplasia and SPEM, studies in Mongolian gerbils have provided additional insights. Mongolian gerbils develop both SPEM and intestinal Metaplasia in the fundus following infection with Helicobacter pylori (15). In Mongolian gerbils, intestinal Metaplasia developed in pre-existing SPEM glands and mixed glands expressing both SPEM and intestinal Metaplasia were clearly present (15). All of these studies have supported the notion that intestinal Metaplasia may develop from pre-existing SPEM. No published studies in humans have addressed directly the question of the relationship of SPEM to intestinal Metaplasia in humans. We have therefore examined the morphological characteristics of SPEM and intestinal Metaplasia in gastric resections specimens exclusively from the fundus. These studies have uncovered several critical observations about the induction of Metaplasias in the stomach. First, SPEM can develop as a very localized phenomenon. Figure 1 demonstrates that SPEM can develop in single or groups of glands surrounded by regions with normal appearing mucous neck cells in the fundic mucosa. At times these SPEM gland groups are associated with adjacent areas with the appearance of mucous neck cell hyperplasia. These regions do not appear to interact with regions of intestinal Metaplasia. The focal phenotype of SPEM glands suggests that they may act as part of a normal local reparative mechanism for the gastric mucosa. Figure 1 Focal early lesions for SPEM induction We have also sought to determine if there is a relationship between SPEM glands and intestinal Metaplasia in gastric resections. Examination of resection sections containing regions of both SPEM and intestinal Metaplasia led to identification of regions with compound glands where SPEM cells were observed in the deep portions of the glands with intestinal metaplastic lineages in the luminal portions of the glands (Figure 2). Thus, goblet cells staining with either Alcian Blue or Muc2 were observed on the luminal aspects of glands that contain PAS-positive and TFF2-staining SPEM at their bases (Figure 2). It is important to emphasise that these were not residual pyloric type glands, since these sections were taken from areas surrounded by corpus mucosa. While we did observe scattered proliferative Ki67-positive cells within SPEM, in regions with intestinal Metaplasia immediately adjacent to or overlying SPEM, we observed strong staining for Ki67 in cells within the region demarcating the zone between SPEM and intestinal Metaplasia (Figure 2). Many of the Ki67-positive cells were also stained for MUC2. Thus, we observed clear evidence for the existence of intestinal Metaplasia emanating from SPEM. The elevated proliferation in intestinal Metaplasia adjacent to SPEM may indicate a transition or secondary differentiation of SPEM into intestinal Metaplasia. Figure 2 Compound glands containing SPEM and Intestinal Metaplasia These data indicate that the standard concept proposed by Professor Correa now merits further expansion or modification (Figure 3). Work in mouse models and human tissue suggests that loss of parietal cells leads initially to the induction of SPEM. With chronic inflammation in the setting of parietal cell loss, SPEM may give rise to a further differentiation into intestinal Metaplasia. This evolution of mucous cell metaplastic lineages has been noted previously for the Ulcer Associated Lineages (UACL) identified in patients with inflammatory bowel disease (16). While these findings create a strategy for the induction and progression of metaplastic lineages in humans, they do not address the actual origin of gastric adenocarcinoma. It is particularly exciting to consider that if SPEM is derived from chief cell transdifferentiation, then chief cells themselves, or a subset of chief cells, represent an unrecognized progenitor population that can be induced in the pathological stomach. Given the more differentiated nature of intestinal Metaplasia, it now seems somewhat less likely that gastric cancer arises from a goblet cell-containing epithelium. Still, we must acknowledge that at present it remains uncertain whether either SPEM or intestinal Metaplasia is a true precursor for cancer. Nevertheless, it seems likely that evolution of intestinal Metaplasia from SPEM may lead to a hyperproliferative state in which the infected and inflamed mucosa may be more susceptible to establishment of deleterious mutations in stem or progenitor populations. Thus, SPEM and intestinal Metaplasia may be commensals for the neoplastic process rather than true direct precursors. Taken together, this work suggests that a broader view of metaplastic initiation and pre-neoplastic progression is merited in evaluating gastric carcinogenesis. Figure 3 A revised model for the evolution of Metaplasia in the stomach
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Current understanding of SPEM and its standing in the preneoplastic process
Gastric Cancer, 2009Co-Authors: Victoria G. Weis, James R. GoldenringAbstract:Gastric cancer is the second leading cause of cancer-related death worldwide, but the details of gastric carcinogenesis remain unclear. In humans, two preneoplastic Metaplasias are associated with the precancerous stomach: intestinal Metaplasia and spasmolytic polypeptide-expressing Metaplasia (SPEM). While mouse models of Helicobacter sp . infection have not shown intestinal Metaplasia, a number of mouse models lead to the evolution of SPEM. In this review, we summarize increasing data that indicates that SPEM arises in the setting of parietal cell loss, either following acute druginduced oxyntic atrophy or in chronic oxyntic atrophy associated with H. felis infection. Importantly, recent investigations support the origin of SPEM through transdifferentiation from mature chief cells following parietal cell loss. Novel biomarkers of SPEM, such as HE4, hold promise as specific markers of the metaplastic process distinct from normal gastric lineages. Staining with HE4 in humans and other studies in gerbils suggest that SPEM arises initially in the human stomach following parietal cell loss and then further evolves into intestinal Metaplasia, likely in association with chronic inflammation. Further studies are needed to broaden our knowledge of Metaplasia and early cancer-specific biomarkers that could give insights into both lineage derivation and preneoplasia detection.
Jong Jae Park - One of the best experts on this subject based on the ideXlab platform.
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Inverted cystic tubulovillous adenoma involving Brunner’s glands of duodenum
World Journal of Gastroenterology, 2007Co-Authors: Jung-woo Choi, Kwan Soo Byun, Jong Eun Yeon, Jong Jae ParkAbstract:Benign neoplasia of the duodenum are very rare. Moreover, duodenal tubulovillous adenomas are more uncommon lesions. The microscopic structure of tubulovillous adenoma has frond-like projection of mucosa with branching papillary structure and generally upward growth into the lumen. We describe a 72-year-old man who showed aduodenal tubulovillous adenoma with unusual inverted cystic growth pattern. Interestingly, this tubulovillous adenomatous lesion was interrupted by gastric Metaplasia in the deep portion of the cyst and was closely surrounded by Brunner’s glands. Although histogenesis of gastric Metaplasia of duodenum is not fully understood, Brunner’s glands has been suggested as a precursor for gastric Metaplasia. Therefore, these findings argued that this adenoma arises from Brunner’s glands through gastric Metaplasia. This is the first case of inverted cystic tubulovillous adenoma involving Brunner’s glands of duodenum with gastric Metaplasia.
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inverted cystic tubulovillous adenoma involving brunner s glands of duodenum
World Journal of Gastroenterology, 2007Co-Authors: Jung-woo Choi, Kwan Soo Byun, Jong Eun Yeon, Jong Jae ParkAbstract:Benign neoplasia of the duodenum are very rare. Moreover, duodenal tubulovillous adenomas are more uncommon lesions. The microscopic structure of tubulovillous adenoma has frond-like projection of mucosa with branching papillary structure and generally upward growth into the lumen. We describe a 72-year-old man who showed aduodenal tubulovillous adenoma with unusual inverted cystic growth pattern. Interestingly, this tubulovillous adenomatous lesion was interrupted by gastric Metaplasia in the deep portion of the cyst and was closely surrounded by Brunner’s glands. Although histogenesis of gastric Metaplasia of duodenum is not fully understood, Brunner’s glands has been suggested as a precursor for gastric Metaplasia. Therefore, these findings argued that this adenoma arises from Brunner’s glands through gastric Metaplasia. This is the first case of inverted cystic tubulovillous adenoma involving Brunner’s glands of duodenum with gastric Metaplasia.
Anil K. Rustgi - One of the best experts on this subject based on the ideXlab platform.
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Metaplasia: tissue injury adaptation and a precursor to the dysplasia–cancer sequence
Nature Reviews Cancer, 2017Co-Authors: Veronique Giroux, Anil K. RustgiAbstract:Metaplasia, the replacement of one differentiated somatic cell type with another in the same tissue, is a precursor to dysplasia and eventually carcinoma. There are shared principles across different types of tissue Metaplasia that may be helpful in clinical considerations. 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. 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.
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Metaplasia: tissue injury adaptation and a precursor to the dysplasia–cancer sequence
Nature Reviews Cancer, 2017Co-Authors: Veronique Giroux, Anil K. RustgiAbstract:Metaplasia, the replacement of one differentiated somatic cell type with another in the same tissue, is a precursor to dysplasia and eventually carcinoma. There are shared principles across different types of tissue Metaplasia that may be helpful in clinical considerations. 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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Metaplasia tissue injury adaptation and a precursor to the dysplasia cancer sequence
Nature Reviews Cancer, 2017Co-Authors: Veronique Giroux, Anil K. RustgiAbstract:Metaplasia, the replacement of one differentiated somatic cell type with another in the same tissue, is a precursor to dysplasia and eventually carcinoma. There are shared principles across different types of tissue Metaplasia that may be helpful in clinical considerations. 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.
Jung-woo Choi - One of the best experts on this subject based on the ideXlab platform.
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Inverted cystic tubulovillous adenoma involving Brunner’s glands of duodenum
World Journal of Gastroenterology, 2007Co-Authors: Jung-woo Choi, Kwan Soo Byun, Jong Eun Yeon, Jong Jae ParkAbstract:Benign neoplasia of the duodenum are very rare. Moreover, duodenal tubulovillous adenomas are more uncommon lesions. The microscopic structure of tubulovillous adenoma has frond-like projection of mucosa with branching papillary structure and generally upward growth into the lumen. We describe a 72-year-old man who showed aduodenal tubulovillous adenoma with unusual inverted cystic growth pattern. Interestingly, this tubulovillous adenomatous lesion was interrupted by gastric Metaplasia in the deep portion of the cyst and was closely surrounded by Brunner’s glands. Although histogenesis of gastric Metaplasia of duodenum is not fully understood, Brunner’s glands has been suggested as a precursor for gastric Metaplasia. Therefore, these findings argued that this adenoma arises from Brunner’s glands through gastric Metaplasia. This is the first case of inverted cystic tubulovillous adenoma involving Brunner’s glands of duodenum with gastric Metaplasia.
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inverted cystic tubulovillous adenoma involving brunner s glands of duodenum
World Journal of Gastroenterology, 2007Co-Authors: Jung-woo Choi, Kwan Soo Byun, Jong Eun Yeon, Jong Jae ParkAbstract:Benign neoplasia of the duodenum are very rare. Moreover, duodenal tubulovillous adenomas are more uncommon lesions. The microscopic structure of tubulovillous adenoma has frond-like projection of mucosa with branching papillary structure and generally upward growth into the lumen. We describe a 72-year-old man who showed aduodenal tubulovillous adenoma with unusual inverted cystic growth pattern. Interestingly, this tubulovillous adenomatous lesion was interrupted by gastric Metaplasia in the deep portion of the cyst and was closely surrounded by Brunner’s glands. Although histogenesis of gastric Metaplasia of duodenum is not fully understood, Brunner’s glands has been suggested as a precursor for gastric Metaplasia. Therefore, these findings argued that this adenoma arises from Brunner’s glands through gastric Metaplasia. This is the first case of inverted cystic tubulovillous adenoma involving Brunner’s glands of duodenum with gastric Metaplasia.
Veronique Giroux - One of the best experts on this subject based on the ideXlab platform.
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Metaplasia: tissue injury adaptation and a precursor to the dysplasia–cancer sequence
Nature Reviews Cancer, 2017Co-Authors: Veronique Giroux, Anil K. RustgiAbstract:Metaplasia, the replacement of one differentiated somatic cell type with another in the same tissue, is a precursor to dysplasia and eventually carcinoma. There are shared principles across different types of tissue Metaplasia that may be helpful in clinical considerations. 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. 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.
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Metaplasia: tissue injury adaptation and a precursor to the dysplasia–cancer sequence
Nature Reviews Cancer, 2017Co-Authors: Veronique Giroux, Anil K. RustgiAbstract:Metaplasia, the replacement of one differentiated somatic cell type with another in the same tissue, is a precursor to dysplasia and eventually carcinoma. There are shared principles across different types of tissue Metaplasia that may be helpful in clinical considerations. 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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Metaplasia tissue injury adaptation and a precursor to the dysplasia cancer sequence
Nature Reviews Cancer, 2017Co-Authors: Veronique Giroux, Anil K. RustgiAbstract:Metaplasia, the replacement of one differentiated somatic cell type with another in the same tissue, is a precursor to dysplasia and eventually carcinoma. There are shared principles across different types of tissue Metaplasia that may be helpful in clinical considerations. 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.
