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Nature Reviews. Cancer Oct 2017Metaplasia is the replacement of one differentiated somatic cell type with another differentiated somatic cell type in the same tissue. Typically, metaplasia is... (Review)
Review
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.
Topics: Adaptation, Biological; Animals; Barrett Esophagus; Epigenesis, Genetic; Epithelium; Gastric Mucosa; Humans; Intestinal Mucosa; Metaplasia; Mucous Membrane; Respiratory Mucosa; Transcription Factors
PubMed: 28860646
DOI: 10.1038/nrc.2017.68 -
The Journal of Physiology Sep 2018The development of intestinal-type gastric cancer is preceded by the emergence of metaplastic cell lineages in the gastric mucosa. In particular, intestinal metaplasia... (Review)
Review
The development of intestinal-type gastric cancer is preceded by the emergence of metaplastic cell lineages in the gastric mucosa. In particular, intestinal metaplasia and spasmolytic polypeptide-expressing metaplasia (SPEM) have been associated with the pathological progression to intestinal-type gastric cancer. The development of SPEM represents a physiological response to damage that recruits reparative cells to sites of mucosal injury. Metaplastic cell lineages are characterized by mucus secretion, adding a protective barrier to the epithelium. Increasing evidence indicates that the influence of alarmins and cytokines is required to initiate the process of metaplasia development. In particular, IL-33 derived from epithelial cells stimulates IL-13 production by specialized innate immune cells to induce chief cell transdifferentiation into SPEM following the loss of parietal cells from the corpus of the stomach. While SPEM represents a physiological healing response to acute injury, persistent injury and chronic inflammation can perpetuate a recurring pattern of reprogramming and metaplasia that is a risk factor for gastric cancer development. The transdifferentiation of zymogen secreting cells into mucous cell metaplasia may represent both a general repair mechanism in response to mucosal injury in many epithelia as well as a common pre-neoplastic pathway associated with chronic injury and inflammation.
Topics: Animals; Humans; Inflammation; Intercellular Signaling Peptides and Proteins; Interleukin-13; Intestines; Metaplasia; Parietal Cells, Gastric; Stomach
PubMed: 29427515
DOI: 10.1113/JP275512 -
Endoscopy Apr 2019Patients with chronic atrophic gastritis or intestinal metaplasia (IM) are at risk for gastric adenocarcinoma. This underscores the importance of diagnosis and risk...
Management of epithelial precancerous conditions and lesions in the stomach (MAPS II): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG), European Society of Pathology (ESP), and Sociedade Portuguesa de Endoscopia Digestiva (SPED)...
Patients with chronic atrophic gastritis or intestinal metaplasia (IM) are at risk for gastric adenocarcinoma. This underscores the importance of diagnosis and risk stratification for these patients. High definition endoscopy with chromoendoscopy (CE) is better than high definition white-light endoscopy alone for this purpose. Virtual CE can guide biopsies for staging atrophic and metaplastic changes and can target neoplastic lesions. Biopsies should be taken from at least two topographic sites (antrum and corpus) and labelled in two separate vials. For patients with mild to moderate atrophy restricted to the antrum there is no evidence to recommend surveillance. In patients with IM at a single location but with a family history of gastric cancer, incomplete IM, or persistent gastritis, endoscopic surveillance with CE and guided biopsies may be considered in 3 years. Patients with advanced stages of atrophic gastritis should be followed up with a high quality endoscopy every 3 years. In patients with dysplasia, in the absence of an endoscopically defined lesion, immediate high quality endoscopic reassessment with CE is recommended. Patients with an endoscopically visible lesion harboring low or high grade dysplasia or carcinoma should undergo staging and treatment. eradication heals nonatrophic chronic gastritis, may lead to regression of atrophic gastritis, and reduces the risk of gastric cancer in patients with these conditions, and it is recommended. eradication is also recommended for patients with neoplasia after endoscopic therapy. In intermediate to high risk regions, identification and surveillance of patients with precancerous gastric conditions is cost-effective.
Topics: Biopsy; Endoscopy, Gastrointestinal; Europe; Gastritis, Atrophic; Helicobacter Infections; Humans; Metaplasia; Patient Care Management; Precancerous Conditions; Risk Assessment; Stomach Neoplasms
PubMed: 30841008
DOI: 10.1055/a-0859-1883 -
Archives of Pathology & Laboratory... Nov 2019Autoimmune gastritis (AG) is a corpus-restricted chronic atrophic gastritis associated with intrinsic factor deficiency, either with or without pernicious anemia.... (Review)
Review
CONTEXT.—
Autoimmune gastritis (AG) is a corpus-restricted chronic atrophic gastritis associated with intrinsic factor deficiency, either with or without pernicious anemia. Autoimmune gastritis is a microscopic disease because patients present with no or vague symptoms, and clinicians rarely find endoscopic changes. Autoimmune gastritis only becomes a clinical disease when pathologists diagnose it in gastric biopsies performed for a variety of clinical indications. Unfamiliarity with this disease can result in misdiagnosis of patients, and thus inadequate patient management.
OBJECTIVE.—
To review the pathogenesis, clinical features, diagnostic criteria, differential diagnoses, sequelae, and surveillance recommendations for AG.
DATA SOURCES.—
The sources of the study include a review of the pertinent literature for AG.
CONCLUSIONS.—
Autoimmune gastritis is an important disease characterized by a loss of oxyntic mucosa and presence of metaplastic epithelium and enterochromaffin-like cell hyperplasia. Awareness and proper diagnosis are critical to prevent mismanagement of patients.
Topics: Anemia, Pernicious; Autoimmune Diseases; Biopsy; Chronic Disease; Diagnosis, Differential; Diagnostic Errors; Epithelium; Gastritis, Atrophic; Humans; Hyperplasia; Intrinsic Factor; Metaplasia; Stomach
PubMed: 31661309
DOI: 10.5858/arpa.2019-0345-RA -
World Journal of Gastroenterology Feb 2020Recent advances in endoscopic technology allow detailed observation of the gastric mucosa. Today, endoscopy is used in the diagnosis of gastritis to determine the... (Review)
Review
Recent advances in endoscopic technology allow detailed observation of the gastric mucosa. Today, endoscopy is used in the diagnosis of gastritis to determine the presence/absence of infection and evaluate gastric cancer risk. In 2013, the Japan Gastroenterological Endoscopy Society advocated the Kyoto classification, a new grading system for endoscopic gastritis. The Kyoto classification organized endoscopic findings related to infection. The Kyoto classification score is the sum of scores for five endoscopic findings (atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness with or without regular arrangement of collecting venules) and ranges from 0 to 8. Atrophy, intestinal metaplasia, enlarged folds, and nodularity contribute to gastric cancer risk. Diffuse redness and regular arrangement of collecting venules are related to infection status. In subjects without a history of eradication, the infection rates in those with Kyoto scores of 0, 1, and ≥ 2 were 1.5%, 45%, and 82%, respectively. A Kyoto classification score of 0 indicates no infection. A Kyoto classification score of 2 or more indicates infection. Kyoto classification scores of patients with and without gastric cancer were 4.8 and 3.8, respectively. A Kyoto classification score of 4 or more might indicate gastric cancer risk.
Topics: Atrophy; Consensus; Gastric Mucosa; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Japan; Metaplasia; Practice Guidelines as Topic; Risk Assessment; Risk Factors; Stomach Neoplasms
PubMed: 32089624
DOI: 10.3748/wjg.v26.i5.466 -
International Journal of Molecular... Jun 2021Prognosis of gastric cancer is dramatically improved by early diagnosis. Correa's cascade correlates the expression of some molecular markers with the progression of... (Review)
Review
Prognosis of gastric cancer is dramatically improved by early diagnosis. Correa's cascade correlates the expression of some molecular markers with the progression of preneoplastic lesions toward carcinoma. This article reviews the diagnostic and prognostic values of molecular markers in complete () and incomplete (, and ) intestinal metaplasia, gastric dysplasia/intra-epithelial neoplasia, and early gastric cancer. In particular, considering preinvasive neoplasia and early gastric cancer, some studies have demonstrated a correlation between molecular alterations and prognosis, for example, mucins phenotype in gastric dysplasia, and GATA6, TP53 mutation/LOH and in early gastric cancer. Moreover, this review considers novelties from the literature regarding the (immuno)histochemical characterization of diffuse-type/signet ring cell gastric cancer, with particular attention to clinical outcomes of patients. The aim of this review is the evaluation of the state of the art regarding suitable biomarkers used in the pre-surgical phase, which can distinguish patients with different prognoses and help decide the best therapeutic strategy.
Topics: Biomarkers, Tumor; Early Detection of Cancer; GATA6 Transcription Factor; Gene Expression Regulation, Neoplastic; Humans; Intestines; Metaplasia; Mucin 5AC; Mucin-2; Mucin-6; Mutation; Prognosis; Stomach Neoplasms; Tumor Suppressor Protein p53
PubMed: 34206291
DOI: 10.3390/ijms22136652 -
Archives of Pathology & Laboratory... May 2022Claudin-18 is expressed in some gastric cancers. Clinical trials are evaluating it as a therapeutic target.
CONTEXT.—
Claudin-18 is expressed in some gastric cancers. Clinical trials are evaluating it as a therapeutic target.
OBJECTIVES.—
To evaluate claudin-18 expression in intestinal metaplasia, dysplasia, and adenocarcinoma of the distal esophagus/gastroesophageal junction and stomach and to evaluate claudin-18 expression in gastric and nongastric neuroendocrine tumors as a marker of gastric origin.
DESIGN.—
Samples included gastroesophageal junction with intestinal metaplasia (n = 40), dysplasia (n = 54), and adenocarcinoma (n = 20) and stomach with intestinal metaplasia (n = 79), dysplasia (n = 43), and adenocarcinoma (n = 25). Additionally, gastric (n = 40) and nongastric (n = 322) neuroendocrine tumors were included. Claudin-18 expression was evaluated for any staining as positive and by meeting clinical trial inclusion criteria (≥2+ intensity in ≥50% of tumor).
RESULTS.—
Claudin-18 staining was not significantly different across dysplasia categories in the gastroesophageal junction (P = .11) or stomach (P = .12). The rate of positive staining was higher in gastroesophageal junction than stomach for intestinal metaplasia (37 of 40 [92.5%] versus 37 of 79 [46.8%]; P < .001) and high-grade dysplasia (33 of 38 [86.8%] versus 9 of 16 [56.3%]; P = .03). Intestinal metaplasia showed staining in 7 of 37 autoimmune gastritis samples (18.9%) compared with 30 of 42 samples without autoimmune gastritis (71.4%) (P < .001). Adenocarcinoma showed similar staining in gastroesophageal junction (15 of 20; 75.0%) and stomach (17 of 25; 68.0%) (P = .85). Eighty percent (32 of 40) of gastric neuroendocrine tumors were positive for claudin-18 expression, with 57.5% (23 of 40) meeting clinical trial inclusion criteria. Comparatively, 0.62% (2 of 322) of nongastric neuroendocrine tumors showed staining (P < .001).
CONCLUSIONS.—
Claudin-18 staining was similar in intestinal metaplasia, dysplasia, and adenocarcinoma. Claudin-18 was negative in most cases of intestinal metaplasia in autoimmune gastritis, indicating that intestinal metaplasia in this setting may differ from other forms. Claudin-18 was sensitive and specific for gastric origin in neuroendocrine tumors.
Topics: Humans; Esophagogastric Junction; Stomach Neoplasms; Gastritis; Adenocarcinoma; Precancerous Conditions; Metaplasia; Hyperplasia; Claudins; Neuroendocrine Tumors
PubMed: 35976638
DOI: 10.5858/arpa.2021-0428-OA -
Breast Cancer Research : BCR Nov 2020Metaplastic breast cancer (MpBC) is an exceedingly rare breast cancer variant that is therapeutically challenging and aggressive. MpBC is defined by the histological... (Review)
Review
Metaplastic breast cancer (MpBC) is an exceedingly rare breast cancer variant that is therapeutically challenging and aggressive. MpBC is defined by the histological presence of at least two cellular types, typically epithelial and mesenchymal components. This variant harbors a triple-negative breast cancer (TNBC) phenotype, yet has a worse prognosis and decreased survival compared to TNBC. There are currently no standardized treatment guidelines specifically for MpBC. However, prior studies have found that MpBC typically has molecular alterations in epithelial-to-mesenchymal transition, amplification of epidermal growth factor receptor, PI3K/Akt signaling, nitric oxide signaling, Wnt/β-catenin signaling, altered immune response, and cell cycle dysregulation. Some of these molecular alterations have been studied as therapeutic targets, in both the preclinical and clinical setting. This current review discusses the histological organization and cellular origins of MpBC, molecular alterations, the role of radiation therapy, and current clinical trials for MpBC.
Topics: Breast Neoplasms; Cell Line, Tumor; Epithelial-Mesenchymal Transition; Female; Genes, Neoplasm; Humans; Metaplasia; Molecular Targeted Therapy; Nitric Oxide Synthase; Phosphatidylinositol 3-Kinases; Triple Negative Breast Neoplasms; Wnt Signaling Pathway
PubMed: 33148288
DOI: 10.1186/s13058-020-01353-z -
BMC Gastroenterology Feb 2014Chronic gastritis is one of the most common findings at upper endoscopy in the general population, and chronic atrophic gastritis is epidemiologically associated with...
BACKGROUND
Chronic gastritis is one of the most common findings at upper endoscopy in the general population, and chronic atrophic gastritis is epidemiologically associated with the occurrence of gastric cancer. However, the current status of diagnosis and treatment of chronic gastritis in China is unclear.
METHODS
A multi-center national study was performed; all patients who underwent diagnostic upper endoscopy for evaluation of gastrointestinal symptoms from 33 centers were enrolled. Data including sex, age, symptoms and endoscopic findings were prospectively recorded.
RESULTS
Totally 8892 patients were included. At endoscopy, 4389, 3760 and 1573 patients were diagnosed to have superficial gastritis, erosive gastritis, and atrophic gastritis, respectively. After pathologic examination, it is found that atrophic gastritis, intestinal metaplasia and dysplasia were prevalent, which accounted for 25.8%, 23.6% and 7.3% of this patient population. Endoscopic features were useful for predicting pathologic atrophy (PLR = 4.78), but it was not useful for predicting erosive gastritis. Mucosal-protective agents and PPI were most commonly used medications for chronic gastritis.
CONCLUSIONS
The present study suggests non-atrophic gastritis is the most common endoscopic finding in Chinese patients with upper GI symptoms. Precancerous lesions, including atrophy, intestinal metaplasia and dysplasia are prevalent in Chinese patients with chronic gastritis, and endoscopic features are useful for predicting pathologic atrophy.
Topics: Adolescent; Adult; Aged; China; Chronic Disease; Endoscopy, Gastrointestinal; Female; Gastritis; Gastritis, Atrophic; Humans; Male; Metaplasia; Middle Aged; Prevalence; Prospective Studies; Proton Pump Inhibitors; Stomach; Young Adult
PubMed: 24502423
DOI: 10.1186/1471-230X-14-21 -
Gastroenterology Jan 2021In stomach, metaplasia can arise from differentiated chief cells that become mitotic via paligenosis, a stepwise program. In paligenosis, mitosis initiation requires...
BACKGROUND AND AIMS
In stomach, metaplasia can arise from differentiated chief cells that become mitotic via paligenosis, a stepwise program. In paligenosis, mitosis initiation requires reactivation of the cellular energy hub mTORC1 after initial mTORC1 suppression by DNA damage induced transcript 4 (DDIT4 aka REDD1). Here, we use DDIT4-deficient mice and human cells to study how metaplasia increases tumorigenesis risk.
METHODS
A tissue microarray of human gastric tissue specimens was analyzed by immunohistochemistry for DDIT4. C57BL/6 mice were administered combinations of intraperitoneal injections of high-dose tamoxifen (TAM) to induce spasmolytic polypeptide-expressing metaplasia (SPEM) and rapamycin to block mTORC1 activity, and N-methyl-N-nitrosourea (MNU) in drinking water to induce spontaneous gastric tumors. Stomachs were analyzed for proliferation, DNA damage, and tumor formation. CRISPR/Cas9-generated DDIT4 and control human gastric cells were analyzed for growth in vitro and in xenografts with and without 5-fluorouracil (5-FU) treatment.
RESULTS
DDIT4 was expressed in normal gastric chief cells in mice and humans and decreased as chief cells became metaplastic. Paligenotic Ddit4 chief cells maintained constitutively high mTORC1, causing increased mitosis of metaplastic cells despite DNA damage. Lower DDIT4 expression correlated with longer survival of patients with gastric cancer. 5-FU-treated DDIT4 human gastric epithelial cells had significantly increased cells entering mitosis despite DNA damage and increased proliferation in vitro and in xenografts. MNU-treated Ddit4 mice had increased spontaneous tumorigenesis after multiple rounds of paligenosis induced by TAM.
CONCLUSIONS
During injury-induced metaplastic proliferation, failure of licensing mTORC1 reactivation correlates with increased proliferation of cells harboring DNA damage, as well as increased tumor formation and growth in mice and humans.
Topics: Animals; Carcinogenesis; Cell Culture Techniques; Cell Proliferation; Chief Cells, Gastric; Humans; Metaplasia; Mice; Mice, Inbred C57BL; Transcription Factors
PubMed: 32956680
DOI: 10.1053/j.gastro.2020.09.016