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Potential Contribution of Epithelial Growth Factor Receptor to PI3K/AKT Pathway Dysregulation in Canine Soft Tissue
Alfarisa Nururrozi1,2, Masaya Igase1,3, Kyohei Miyanishi1
1Laboratory of Molecular Diagnostics and Therapeutics, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.
Background/Aim:
Soft tissue sarcoma (STS) is a mesenchymal tumor affecting multiple organs in dogs. Previous studies identified activation of the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (PKB, AKT) pathway in canine STS cell lines and clinical samples, but the underlying mechanism remains unclear. This study investigated PTEN loss, PIK3CA mutation, and EGFR over-expression as potential drivers of PI3K/AKT pathway activation in STS.
Materials And Methods:
We analyzed 36 canine STS samples. PTEN and EGFR expression were evaluated using immunohistochemistry, while PIK3CA and EGFR mutations were assessed through DNA sequencing.
Results:
PTEN was expressed in all analyzed samples, with no evidence of loss. Weak PTEN expression was observed in 12 (33.3%) samples, while 24 (66.7%) showed normal expression. DNA sequencing of PIK3CA revealed a single point mutation (c.554 A>C, H554P) in one case, but no hotspot mutations were identified. High EGFR expression was significantly correlated with elevated phospho-AKT levels (p<0.0001). Immunolabelling indicated that 30 samples (83.3%) were EGFR-positive, and 27 of these also showed positive phospho-AKT labeling. Accordingly, one missense point mutation in exon 21 of EGFR (E868K) was identified in one of 12 samples.
Conclusion:
EGFR over-expression, rather than PTEN loss or PIK3CA mutations, may contribute to PI3K/AKT pathway dysregulation in canine STS. Further studies with larger sample sizes and additional validation techniques are necessary to confirm these findings.
Insights
EGFR over-expression, not PTEN loss or PIK3CA mutations, may drive the PI3K/AKT pathway in canine soft tissue sarcoma (STS). Further research is needed to confirm these findings in canine STS.
Area of Science:
- Veterinary Oncology
- Molecular Pathology
- Canine Cancer Research
Background:
- Soft tissue sarcoma (STS) is a common mesenchymal tumor in dogs.
- The phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) pathway is often activated in canine STS.
- The specific molecular mechanisms driving this pathway activation are not fully understood.
Purpose of the Study:
- To investigate the roles of PTEN loss, PIK3CA mutation, and EGFR over-expression in PI3K/AKT pathway activation in canine STS.
- To identify potential therapeutic targets for canine STS.
Main Methods:
- Analysis of 36 canine STS samples.
- Immunohistochemistry for PTEN and EGFR expression.
- DNA sequencing for PIK3CA and EGFR mutations.
Main Results:
- PTEN loss was not observed; however, weak PTEN expression was present in 33.3% of samples.
- A single PIK3CA mutation was found in one sample; no hotspot mutations were identified.
- High EGFR expression strongly correlated with elevated phospho-AKT levels (p<0.0001), with 83.3% of samples showing EGFR positivity and 90% of those also exhibiting phospho-AKT positivity.
Conclusions:
- EGFR over-expression appears to be a significant factor in PI3K/AKT pathway dysregulation in canine STS.
- PTEN loss and PIK3CA mutations are less likely contributors.
- Larger studies are required to validate these findings and explore therapeutic strategies targeting EGFR in canine STS.
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