Intestinal metaplasia in Barrett's oesophagus may be an epiphenomenon rather than a preneoplastic condition, and <scp>CDX</scp>2‐positive cardiac‐type epithelium is associated with minute Barrett's tumour

Watanabe, Gen; Ajioka, Yoichi; Takeuchi, Manabu; Alexey, Annenkov; Kato, Takashi; Watanabe, Kaori; Tani, Yasuhiro; Ikegami, Kikuo; Yokota, Yoko; Fukuda, Mutsumi

doi:10.1111/his.12486

Cited by 8 publications

(6 citation statements)

References 51 publications

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“…In a recent study by Lavery et al , development of adenocarcinoma from premalignant columnar epithelium without goblet cells was convincingly demonstrated by tracing the clonal origin of cancer across an entire Barrett’s segment via a combination of histopathologic spatial mapping and clonal ordering 36. The non-goblet columnar epithelium, mainly cardiac-type mucosa, shows molecular abnormalities and the potential for neoplastic progression 28–36 218 224 270. A small prospective study also showed that development of adenocarcinoma in patients with the columnar metaplastic mucosa without IM 271.…”

Section: Resultsmentioning

confidence: 96%

“…The criteria used in the USA suggest that metaplastic columnar epithelium with goblet cells is the main precursor of dysplasia and cancer, and as such, represents the specific subgroup of patients with columnar lined oesophagus at highest risk for neoplastic progression2 267–269 (see also textural explanation for CQ 1). While it is true that most cancers arise in the columnar lined oesophagus with goblet cells, there is indisputable evidence that metaplastic non-goblet columnar mucosa is at risk for cancer 31–35 221. In a recent study by Lavery et al , development of adenocarcinoma from premalignant columnar epithelium without goblet cells was convincingly demonstrated by tracing the clonal origin of cancer across an entire Barrett’s segment via a combination of histopathologic spatial mapping and clonal ordering 36.…”

Section: Resultsmentioning

confidence: 99%

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Kyoto international consensus report on anatomy, pathophysiology and clinical significance of the gastro-oesophageal junction

Sugano

Spechler

El-Omar

et al. 2022

Gut

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ObjectiveAn international meeting was organised to develop consensus on (1) the landmarks to define the gastro-oesophageal junction (GOJ), (2) the occurrence and pathophysiological significance of the cardiac gland, (3) the definition of the gastro-oesophageal junctional zone (GOJZ) and (4) the causes of inflammation, metaplasia and neoplasia occurring in the GOJZ.DesignClinical questions relevant to the afore-mentioned major issues were drafted for which expert panels formulated relevant statements and textural explanations.A Delphi method using an anonymous system was employed to develop the consensus, the level of which was predefined as ≥80% of agreement. Two rounds of voting and amendments were completed before the meeting at which clinical questions and consensus were finalised.ResultsTwenty eight clinical questions and statements were finalised after extensive amendments. Critical consensus was achieved: (1) definition for the GOJ, (2) definition of the GOJZ spanning 1 cm proximal and distal to the GOJ as defined by the end of palisade vessels was accepted based on the anatomical distribution of cardiac type gland, (3) chemical and bacterial (Helicobacter pylori) factors as the primary causes of inflammation, metaplasia and neoplasia occurring in the GOJZ, (4) a new definition of Barrett’s oesophagus (BO).ConclusionsThis international consensus on the new definitions of BO, GOJ and the GOJZ will be instrumental in future studies aiming to resolve many issues on this important anatomic area and hopefully will lead to better classification and management of the diseases surrounding the GOJ.

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Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Kyoto international consensus report on anatomy, pathophysiology and clinical significance of the gastro-oesophageal junction

Sugano

Spechler

El-Omar

et al. 2022

Gut

View full text Add to dashboard Cite

show abstract

“…As discussed, several studies showed that mixed histotype is associated with aggressive behavior, such as tumor size, lymphatic invasion, and lymph node metastasis (23,29,30). On the other hand, Zhong et al (26), in a retrospective study on a total of 298 patients, stated that histological mixed type was not an independent risk factor for lymph node metastasis and was not associated with more aggressive characteristics in comparison with other histotypes.…”

Section: Discussionmentioning

confidence: 99%

The Percentage of Signet Ring Cells Is Inversely Related to Aggressive Behavior and Poor Prognosis in Mixed-Type Gastric Cancer

et al. 2022

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Background and ObjectivesOnly recently the percentage of signet ring cells (SRCs) in gastric cancer (GC) has been proposed as an independent predictor of survival. High amounts of SRCs have been related to lower recurrence and mortality rates, better prognosis, and favorable clinicopathological features in a poorly cohesive histotype. It is not known what the effect of SRC percentage in mixed-type GC is. We investigate the role of SRCs as a prognostic marker in mixed-histotype GC.MethodsA retrospective analysis was performed through a prospectively maintained database of patients with diagnosed “mixed-type” gastric carcinoma, defined according to 2019 WHO classification. These patients underwent surgery between 1995 and 2016, and their tissue samples were stored in a tissue bank. All slides were analyzed, and patients were divided into three groups according to the percentage of SRCs: “Group 1” (displaying ≤10% of SRCs), “Group 2” (displaying <90% but >10% of SRCs), and “Group 3” (displaying ≥90% of SRCs). We compared clinical and pathological features as well as prognostic factors between the different groups.ResultsAmong 164 enrolled patients, 68.9% were male and 31.1% were female (p = 0.612). The mean (±SD) age at diagnosis was 71.4 ± 9.6 years. Ninety-eight (59.7%) patients were classified as “Group 1”, 66 (40.3%) as “Group 2”, and none as “Group 3”. Five-year overall survival was remarkably higher in Group 2 (73.8%) in comparison to Group 1 (35.4%), p < 0.001. Mortality risk was three times higher in patients with ≤10% SRC pattern compared to those with >10% [HR 2.70 (95% CI 1.72–4.24)]. After adjusting according to potential confounding factors, SRC percentage was still an independent predictor of survival.ConclusionsThe proportion of SRCs is inversely related to aggressive behavior and poor prognosis in mixed-type GCs, highlighting the role of SRC amount as an independent predictor of survival.

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“…Takubo K. et al 35 demonstrated that more than 70% cases of minute EAC arise at background of cardiac or fundic‐type metaplasia surrounding the tumor. Performing IHC examination Watanabe G. et al 36 detected gastric phenotype (expression of gastric differentiation markers MUC5A and MUC6 with negative expression of intestinal markers) more frequently in minute tumors. Several phenotypes of dysplasia and EAC were identified based on IHC examination with gastric and intestinal markers that confirm presence of two distinct pathways in carcinogenesis: intestinal and foveolar, 37 , 38 although genetic analysis showed that both metaplasia types harbor the same mutations.…”

Section: Risk Of Eac In Metaplastic Processes Of the Esophagusmentioning

confidence: 99%

Barrett's esophagus: The pathomorphological and molecular genetic keystones of neoplastic progression

et al. 2021

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Barrett's esophagus is a widespread chronically progressing disease of heterogeneous nature. A life threatening complication of this condition is neoplastic transformation, which is often overlooked due to lack of standardized approaches in diagnosis, preventative measures and treatment. In this essay, we aim to stratify existing data to show specific associations between neoplastic transformation and the underlying processes which predate cancerous transition. We discuss pathomorphological, genetic, epigenetic, molecular and immunohistochemical methods related to neoplasia detection on the basis of Barrett's esophagus. Our review sheds light on pathways of such neoplastic progression in the distal esophagus, providing valuable insight into progression assessment, preventative targets and treatment modalities. Our results suggest that molecular, genetic and epigenetic alterations in the esophagus arise earlier than cancerous transformation, meaning the discussed targets can help form preventative strategies in at-risk patient groups.

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Intestinal metaplasia in Barrett's oesophagus may be an epiphenomenon rather than a preneoplastic condition, and CDX2‐positive cardiac‐type epithelium is associated with minute Barrett's tumour

Cited by 8 publications

References 51 publications

Kyoto international consensus report on anatomy, pathophysiology and clinical significance of the gastro-oesophageal junction

Kyoto international consensus report on anatomy, pathophysiology and clinical significance of the gastro-oesophageal junction

The Percentage of Signet Ring Cells Is Inversely Related to Aggressive Behavior and Poor Prognosis in Mixed-Type Gastric Cancer

Barrett's esophagus: The pathomorphological and molecular genetic keystones of neoplastic progression

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