Journal of Pathology and Translational Medicine

Original Articles

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

2,511 View
216 Download
2 Web of Science
2 Crossref

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.

Citations

Citations to this article as recorded by

A review of potential mechanisms and treatments of gastric intestinal metaplasia
Yueyao Wu, Kehan Zhang, Yichao Zheng, Haifeng Jin
European Journal of Gastroenterology & Hepatology.2025; 37(4): 383. CrossRef
Refining NTRK Fusion Detection in Papillary Thyroid Carcinoma Through Pan-TRK Immunohistochemistry and Histopathologic Features
Hyun Lee, Sue Youn Kim, Ji Min Park, Seung-Hyun Jung, Ozgur Mete, Chan Kwon Jung
Endocrine Pathology.2025;[Epub] CrossRef

The Loss of E-cadherin is Associated with the Epigenetic Alteration of CDH1 in Breast Cancer and it is also Associated with an Abnormal beta-catenin Expression in Lobular Carcinoma.: Gwangil Kim, Ji Young Kim, Hee Jung An, Haeyoun Kang, Tae Heon Kim, Jung Yon Shim, Jin Hyung Heo, Hai Lin Park, Young Kil Choi; Korean J Pathol. 2009;43(5):400-407.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.400

3,680 View
38 Download
1 Crossref

Abstract PDF

BACKGROUND
APC and E-cadherin are the key molecules in the Wnt/beta-catenin pathway. We attempted to define the epigenetic alteration of APC and CDH1 (the E-cadherin gene) and the expression of Wnt-related molecules in human mammary carcinomas.
METHODS
Sixty-four mammary carcinomas, including 52 invasive ductal carcinomas (IDCs) and 12 invasive lobular carcinomas (ILCs), were evaluated using methylation-specific PCR and immunohistochemistry. We performed immunohistochemistry for E-cadherin, beta-catenin, APC, Wnt1, cyclin D1, ER, PR and C-erb B2.
RESULTS
Hypermethylation of APC and CDH1 was observed in 38 (59%) and 28 (44%) cases, respectively. CDH1 hypermethylation in ILCs was increased compared to that in IDCs (p=0.002) and it was associated with the loss of E-cadherin (p=0.02) and beta-catenin (p=0.042). APC methylation was positively correlated with the ER expression (p=0.021). Abnormal cytoplasmic localization of beta-catenin was found in 10 cases and any expression was not detected in six cases. In ILCs, the E-cadherin or beta-catenin expression was markedly decreased compared to that in IDCs (p<0.001 in both).
CONCLUSIONS
Methylation of APC or CDH1 was relatively frequent in mammary carcinomas. The loss of E-cadherin in mammary carcinoma was associated with CDH1 methylation, and abnormal beta-catenin expression was related to the loss of E-cadherin in ILC.

Citations

Citations to this article as recorded by

Wnt/β-catenin signaling pathway activation reverses gemcitabine resistance by attenuating Beclin1-mediated autophagy in the MG63 human osteosarcoma cell line
Hao Tao, Feng Chen, Haifei Liu, Yanling Hu, Yingzhen Wang, Haiyan Li
Molecular Medicine Reports.2017; 16(2): 1701. CrossRef

Genetic and Epigenetic Alterations of the Wnt/beta-catenin Signaling Pathway in Cancer of the Ampulla of Vater.: Gwang Il Kim, Jeong Boon Kim, Sang Bum Park, Young Sik Kim, Han Kyeom Kim, Bom Woo Yeom, Yang Seok Chae; Korean J Pathol. 2007;41(4):224-231.

2,256 View
32 Download

Abstract PDF: BACKGROUND
Carcinoma of the ampulla of Vater is rare and its pathogenesis is unclear. The role of epigenetic changes in the APC or CDH1, in the Wnt pathway, has not been reported in ampullary carcinomas.
METHODS
We performed immunohistochemistry on 73 sporadic ampullary carcinomas to identify Wnt-related molecules (APC, beta-catenin, E-cadherin, c-erbB2, cyclin D1) and examined mutations in the CTNNB1, loss of heterozygosity of 5q21, and the methylation status of the CpG island of APC and CDH1.
RESULTS
Thirteen tumors (17.8%) showed abnormal nuclear localization of beta-catenin; this was more prominent in the intestinal type than in the pancreaticobiliary type (p=0.01). The loss of APC correlated with the loss of beta-catenin or c-erb B2 (p<0.01). The prognosis was worse in the group with APC loss than when APC was maintained (p<0.05). There was no mutation identified in CTNNB1. Six (24%) out of 25 informative cases had 5q21 allelic loss. CpG island methylation in APC and CDH1 was detected in 33 (45.2%) and 29 (31.5%) cases, respectively.
CONCLUSIONS
The absence of mutations in CTNNB1 and the epigenetic alteration of APC and CDH1, might be characteristic changes in the Wnt/beta-catenin signaling pathway during the carcinogenesis of ampullary carcinomas.

First
Prev
Page of 1
Next
Last

Search