J Pathol Transl Med.  2023 Nov;57(6):315-322. 10.4132/jptm.2023.10.12.

Elevated expression of Axin2 in intestinal metaplasia and gastric cancers

• Lee DH
• Jeong IH
• Jang B

• KMID: 2547929
• DOI: http://doi.org/10.4132/jptm.2023.10.12

Abstract

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.

Keyword

Wnt signaling pathway; Axin2; β-catenin; Gastric carcinoma; Intestinal metaplasia

Figure

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  Fig. 1. Axin2 expression in normal gastric mucosa. Normal antrum and corpus show focal Axin2 expression (intensity level 2) in the superficial and isthmic areas.

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  Fig. 2. Axin2 expression in gastric mucosa with chronic gastritis. Focal axin2 expression (intensity level 2) is observed in the superficial and isthmic areas of the antrum and corpus.

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  Fig. 3. Increased Axin2 expression in intestinal metaplasia (IM). (A) IM lesions in the antrum and corpus show enhanced Axin2 expression (intensity level 2–3) mainly at the bases. (B) A bar graph showing histo-scores (H-scores) of Axin2 in the non-cancerous stomach tissues, including normal gastric tissue, chronic gastritis, and IM cases. *p < .05.

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  Fig. 4. Axin2 expression in gastric carcinomas according to Lauren classification. Representative intestinal (A) and diffuse type (B) gastric carcinomas showing high or low Axin2 expression. Red dotted lines indicate the border between normal gastric mucosa and gastric carcinoma. Black dotted boxes denote enlarged areas.

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  Fig. 5. Associations between Axin2 and nuclear β-catenin (nuc β-catenin) expression in gastric carcinomas. Representative cases showing low Axin2 and negative nuclear β-catenin expression (A) and high Axin2 and positive nuclear β-catenin expression (B) in gastric carcinomas. (C) A bar graph showing histo-scores (H-scores) of Axin2 in gastric carcinomas with negative nuclear β-catenin expression or positive nuclear β-catenin expression. ****p < .0001.

Reference

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