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Published on: July 25, 2020
PIK3CA alterations in Middle Eastern ovarian cancers
Jehad Abubaker1, Prashant Bavi, Wael Al-Haqawi
1Department of Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. jabubakr@kfshrc.edu.sa
Background:
PI3K/AKTsignaling pathway plays an important role in cell growth, proliferation, and tumorgenesis of various malignancies. This signaling pathway has been shown to be frequently altered in several human cancers including ovarian cancers. However the role of this oncogenic signaling pathway has not been explored in the Middle Eastern epithelial ovarian cancer (EOC). Therefore, we investigated PI3K/AKT genetic alterations such as PIK3CA amplification, PIK3CA mutation, PTEN protein loss and their relationships with various clinicopathological characteristics in 156 EOCs.
Results:
Fluorescence in situ hybridization (FISH) technique and DNA sequencing were used to analyze PIK3CA amplification and mutation respectively. Expression of PIK3CA protein expression (p110 alpha), PTEN, p-AKT and Ki-67 was analyzed by immunohistochemistry. PIK3CA amplification was seen in 54 of 152 (35.5%) EOC cases analyzed; PIK3CA gene mutations in 6/153 EOC (3.9%); KRAS mutations in 3/154 EOC (1.9%), BRAF mutations in 3/156 EOC (1.9%), p53 mutation in 50/154 EOC (32.5%), and loss of PTEN protein expression in 33/144 EOC (22.9%). p110 alpha overexpression was associated with increased phosphorylation of AKT-Ser 473 and with the proliferation marker Ki-67.
Conclusion:
Our data showed mutual exclusivity between the molecular event of PIK3CA amplification and mutations in PIK3CA, KRAS, BRAF genes, which suggests that each of these alterations may individually be sufficient to drive ovarian tumor pathogenesis independently. High prevalence of genetic alterations in PI3K/AKT pathway in a Middle Eastern ovarian carcinoma provides genetic evidence supporting the notion that dysregulated PI3K/AKT pathways play an important role in the pathogenesis of ovarian cancers.
Insights
Genetic alterations in the PI3K/AKT pathway are common in Middle Eastern epithelial ovarian cancer (EOC). These molecular events, including PIK3CA amplification, drive ovarian tumor development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The PI3K/AKT signaling pathway is crucial for cell growth and tumorgenesis.
- This pathway is frequently altered in various cancers, including ovarian cancer.
- Its role in Middle Eastern epithelial ovarian cancer (EOC) remains underexplored.
Purpose of the Study:
- To investigate PI3K/AKT pathway genetic alterations in Middle Eastern EOC.
- To analyze PIK3CA amplification, PIK3CA mutation, and PTEN protein loss.
- To correlate these alterations with clinicopathological characteristics.
Main Methods:
- Fluorescence in situ hybridization (FISH) for PIK3CA amplification.
- DNA sequencing for gene mutations (PIK3CA, KRAS, BRAF, p53).
- Immunohistochemistry for protein expression (PIK3CA, PTEN, p-AKT, Ki-67).
Main Results:
- PIK3CA amplification occurred in 35.5% of EOC cases.
- PIK3CA mutations (3.9%), KRAS (1.9%), BRAF (1.9%), and p53 (32.5%) mutations were observed.
- PTEN protein loss was found in 22.9% of cases; p110 alpha overexpression correlated with AKT phosphorylation and Ki-67.
Conclusions:
- PIK3CA amplification and gene mutations are mutually exclusive, suggesting independent roles in pathogenesis.
- High prevalence of PI3K/AKT pathway alterations supports its significant role in EOC development.
- These findings highlight the importance of the PI3K/AKT pathway in Middle Eastern ovarian carcinoma.
