Send to

Choose Destination
J BUON. 2019 Jan-Feb;24(1):329-337.

PI3K/AKT pathway genetic alterations and dysregulation of expression in bladder cancer.

Author information

2nd Department of Urology, Sismanogleion General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.



To examine the involvement of specific components of the PI3K/AKT pathway in urinary bladder cancer development.


Samples from 65 tumors and 13 normal bladder tissues were collected. Genomic DNA isolation from snap-frozen and paraffin-embedded laser-microdissected tissues was followed by Sanger sequencing, whereas total RNA was purified for use in RT-PCR analyses. Immunohistochemistry was carried out on sections of paraffin-embedded biopsy material.


Three pathogenic mutations (two missense and one frameshift) were identified in exon 20 of PIK3CA {c.3140A>G (p.His1047Arg), c.[3172A>T(;)3174C>T] (p.lle1058Phe), c.3203dupA (p.Asn1068Lysfs*5)} after laser capture microdissection, whereas PTEN mRNA expression was found to be downregulated in bladder cancer tissues compared to normal bladder urothelium. Upregulation of cytoplasmic and nuclear p-AKT expression was detected in low grade tumors, whereas in infiltrating carcinomas p-AKT was shown to be downregulated and confined to the cytoplasm. PTEN expression was weak and mainly cytoplasmic in superficial tumors, but stronger and nuclear in the infiltrating tumors.


PI3K/AKT pathway activation is crucial for bladder cancer initiation and progression. In this context, PIK3CA, p-AKT and nuclear PTEN could be used along with other biomarkers for prognosis and selection of appropriate therapy in the clinical management of bladder cancer.


Supplemental Content

Loading ...
Support Center