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Original Article
- Elevated expression of Axin2 in intestinal metaplasia and gastric cancers
- Dong Hui Lee, In Ho Jeong, Bogun Jang
- J Pathol Transl Med. 2023;57(6):315-322. Published online November 7, 2023
- DOI: https://doi.org/10.4132/jptm.2023.10.12
- 879 View
- 191 Download
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Abstract
PDF - Background
The Wnt signaling pathway regulates crucial cellular processes, including stem cell development and tissue repair. Dysregulation of this pathway, particularly β-catenin stabilization, is linked to colorectal carcinoma and other tumors. Axin2, a critical component in the pathway, plays a role in β-catenin regulation. This study examines Axin2 expression in normal gastric mucosa and various gastric pathologies.
Methods
Formalin-fixed and paraffin-embedded tissue samples from normal stomach, gastritis, intestinal metaplasia (IM), and gastric carcinoma were collected. Axin2 and β-catenin expression were evaluated using RNA in situ hybridization and immunohistochemistry, respectively. Histo-scores (H-scores) were calculated to quantify expression levels of Axin2. Associations between Axin2 expression and clinicopathological variables were examined.
Results
Axin2 expression was examined in normal stomach, gastritis, and IM tissues. Axin2 expression was mainly observed in the surface and isthmus areas in the normal stomach and gastritis, whereas Axin2 expression was markedly higher at the bases of IM. Axin2 H-scores were significantly elevated in IM (mean ± standard deviation [SD], 87.0 ± 38.9) compared to normal (mean ± SD, 18.0 ± 4.5) and gastritis tissues (mean ± SD, 33.0 ± 18.6). In total, 30% of gastric carcinomas showed higher Axin2 expression. Axin2 expression did not have significant associations with age, sex, Lauren classification, histological differentiation, invasion depth, and lymph node metastasis. However, a strong positive correlation was observed between Axin2 and nuclear β-catenin in gastric carcinomas (p < .001).
Conclusions
Axin2 expression was significantly increased in IM compared to normal and gastritis cases. In addition, Axin2 showed a strong positive association with nuclear β-catenin expression in gastric carcinomas, demonstrating a close relationship with abnormal Wnt/β-catenin signaling pathway.
Review
- CpG Island Hypermethylation in Gastric Carcinoma and Its Premalignant Lesions
- Gyeong Hoon Kang
- Korean J Pathol. 2012;46(1):1-9. Published online February 23, 2012
- DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.1
- 7,761 View
- 45 Download
- 18 Crossref
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Abstract
PDF
Gastric cancers arise through a multistep process characterized by the progressive accumulation of molecular alterations in which genetic and epigenetic mechanisms have been implicated. Gastric cancer is one of the human malignancies in which aberrant promoter CpG island hypermethylation is frequently found.
Helicobacter pylori and Epstein-Barr virus, which are known carcinogens for gastric cancer, are closely associated with enhanced hypermethylation of CpG island loci in gastric non-neoplastic epithelial cells and cancer cells, respectively. Aberrant CpG island hypermethylation occurs early in the multistep cascade of gastric carcinogenesis and tends to increase with the step-wise progression of the lesion. Approximately 400 genes that are actively expressed in normal gastric epithelial cells are estimated to be inactivated in gastric cancers as a result of promoter CpG island hypermethylation. In this review, a variety of information is summarized regarding CpG island hypermethylation in gastric cancer.-
Citations
Citations to this article as recorded by
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- Genome-wide characterization of extrachromosomal circular DNA in gastric cancer and its potential role in carcinogenesis and cancer progression
Original Articles
- Helicobacter pylori Infection and Histopathological Features of Gastric Mucosa.
- Gyung Hyuck Ko, Cheol Keun Park, Chun Sik Choi, Heung Bae Park, Jeong Hee Lee, Hye Jung Lee, Hyun Ju Kim, Kwang Ho Rhee
- Korean J Pathol. 1996;30(3):199-209.
- 1,606 View
- 14 Download
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Abstract
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- A microscopic examination of 1,000 cases of gastroscopic biopsy specimens revealed that the prevalence and severity of chronic gastritis, neutrophilic infiltration, and Helicobacter pylori infection increased with advancing age until the age reached about 40, but they decreased thereafter in accordance with the increasing prevalence of intestinal metaplasia. The prevalence and severity of Helicobacter pylori infection, chronic gastritis, and neutrophilic infiltration were proportionately related to each other and to gastric peptic ulcer, but inversely related with intestinal metaplasia and gastric carcinoma. The results suggested that chronic gastritis and gastric peptic ulcer may be associated with Helicobacter pylori infection and that if these lesions persist, intestinal metaplasia may develop with decreased severity of chronic gastritis and Helicobacter pylori infection but, instead, increase of the risk of gastric carcinoma. And it is thought that the cause of the high incidence of gastric carcinoma in Korea may be related to the fact that chronic gastritis and Helicobacter pylori infection develop earlier in life and therefore the prevalence of intestinal metaplasia is higher in Korea than in other countries.
- Correlation of the Intestinal Metaplasia Subtypes and Gastric Carcinoma.
- Hwa Eun Oh, Mee Ja Park, Jong Sang Choi
- Korean J Pathol. 1997;31(12):1272-1281.
- 1,615 View
- 17 Download
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Abstract
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- Helicobacter pylori, loss of basement membrane, atrophy, type III intestinal metaplasia, adenomatous polyposis coli (APC) gene mutations and altered p53 function were believed as a factor to develop the gastric adenocarcinomas. To investigate the incidence and prevalence of Helicobacter pylori, intestinal metaplasia and atrophy, 120 gastrectomy specimens collected from patients with gastric adenocarcinoma (100 cases) and non-neoplastic conditions (20 cases) were studied. Intestinal metaplasia can be classified as type I (complete), type II (incomplete, sulfomucin-negative) and type III (incomplete, sulfomucin-positive) by Filipe and Jass. The incidence of intestinal metaplasia of gastric adenocarcinoma was 96% compared with the incidence of 75% in non-neoplastic conditions. The type I and type II were more common than type III and were present in both non-neoplastic conditions (75%) and adenocarcinoma (74%). In contrast, type III intestinal metaplasia was seen in only 20% of intestinal metaplasia-positive cases, all of which (22 of 22) were from patients with adenocarcinoma. The high specificity of type III intestinal metaplasia might be acceptable for screening purposes, but its sensitivity of 22% for gastric adenocarcinoma is low. Helicobacter pylori were detected in 96% of adenocarcinoma cases and 100% of non-neoplastic cases. Atrophy was detected in 50% of non-neoplastic cases and in 57% of adenocarcinoma cases. The data thus confirms a significant relation between incomplete sulfomucin-secreting intestinal metaplasia (type III) and gastric carcinoma, especially intestinal type (p<0.01). Thus, the type III intestinal metaplasia should be considered a risk factor and its presence in a biopsy specimen should prompt close surveillance.
- An Image Analytical Study on the Structural Spectrum of Intestinal Metaplasia-Dysplasia-Carcinoma of the Stomach.
- Sang Woo Juhng, Dong Ha Park, Ji Shin Lee, Kyu Hyuk Cho
- Korean J Pathol. 1993;27(1):50-57.
- 1,547 View
- 12 Download
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Abstract
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- Intestinal metaplasia and dysplasia of the stomach have been stressed as precursors of gastric carcinoma of the intestinal type, although their preneoplastic nature is still debated. In this study, the cytomorphometric and cytokinetic spectra of the suggested preneoplastic and neoplastic lesions of the stomach were investigated. From the resected stomachs of early gastric carcinoma of intestinal type, areas of normal, intestinal metaplasia, dysplasia, and carcinoma were selected. They were immunostained for proliferating cell nuclear antigen, counterstained with propidium iodide, and various nuclear parameters were measured by image analysis. Normal and intestinal metaplastic mucosae differed by the localization of proliferation zone, but not by nuclear profile area, circular shape factor, and proliferation index. In dysplasia, proliferation zone covered large parts of the dysplastic area. Nuclear profile area and proliferation index were larger whereas circular shape factor was smaller than in normal or intestinal metaplasia. Carcinomatous lesion had diffuse proliferation activity, the largest nuclear profile area and proliferating index, and circular shape factor in-between those of normal or intestinal metaplasia and dysplasia. The above results showed a structural spectrum among normal of intestinal metaplasia, dysplasia, and carcinoma of intestinal type in cytomorphometric and cytokinetic terms. The structural spectrum raises the possibility that dysplasia of the stomach is a preneoplastic lesion.
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