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Akt and Hippo Pathways in Ewing's Sarcoma Tumors and Their Prognostic Significance
Atif A Ahmed1, Malak Abedalthagafi1, Ahmed E Anwar2
11. Department of Pathology, King Fahad Medical City, Riyadh, Saudi Arabia.
Background:
Ewing's sarcoma tumor is an aggressive malignancy of bone and soft tissue in children and young adults. Despite advances in modern therapy, metastasis occurs and results in high mortality. Intracellular molecules Yap, Akt, mTOR, and Erk are signaling pathway members that regulate the proliferation of tumor cells.
Objective And Methods:
We studied the immunohistochemical expression of these proteins in 36 tumor samples from adult and pediatric patients with Ewing's sarcoma tumors. Patients' age, sex, tumor site, tumor size, clinical stage and survival (overall and disease-free survival) were collected. Tissue microarrays slides were stained with antibodies against Yap, Akt, mTOR, and Erk proteins.
Results:
Tumors exhibited variable expression of Yap, Akt, mTOR, and Erk (from negative, low to high), with high levels of expression present in 31%, 53%, 77% and 0% respectively. Immunohistochemical expression of Akt was associated with worse overall and disease-free survival (p<0.05). The other biomarkers did not demonstrate any difference in survival between low versus high expression.
Conclusion:
Although Yap, Akt, mTOR, and Erk protein are all expressed in Ewing's sarcoma by immunohistochemistry, only Akt expression is associated with worse prognosis. Larger studies are needed to verify these results and plan targeted therapy, particularly against Akt.
Insights
High Akt protein expression in Ewing's sarcoma correlates with poorer survival. Yap, mTOR, and Erk showed variable expression but no survival link, suggesting Akt as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Ewing's sarcoma is an aggressive pediatric and young adult cancer with high mortality due to metastasis.
- Intracellular signaling molecules Yap, Akt, mTOR, and Erk regulate tumor cell proliferation.
Purpose of the Study:
- To investigate the immunohistochemical expression of Yap, Akt, mTOR, and Erk in Ewing's sarcoma.
- To correlate protein expression with patient survival outcomes.
Main Methods:
- Analyzed 36 Ewing's sarcoma tumor samples from adult and pediatric patients.
- Utilized immunohistochemistry to assess Yap, Akt, mTOR, and Erk protein expression.
- Collected clinical data including age, sex, tumor characteristics, and survival data.
Main Results:
- Variable expression of Yap, Akt, mTOR, and Erk was observed.
- High Akt expression was found in 53% of tumors and linked to worse overall and disease-free survival (p<0.05).
- Yap, mTOR, and Erk expression levels did not correlate with survival differences.
Conclusions:
- Akt protein expression is a significant prognostic marker in Ewing's sarcoma.
- Targeted therapy against Akt may improve outcomes for patients with Ewing's sarcoma.
- Further research with larger cohorts is necessary to validate these findings.
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