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

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

Author information

1
2nd Department of Urology, Sismanogleion General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Abstract

PURPOSE:

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

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

PMID:
30941989

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