Potential Contribution of Epithelial Growth Factor Receptor to PI3K/AKT Pathway Dysregulation in Canine Soft Tissue Sarcoma.

Abstract

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.