TP53 gene mutations as an independent marker for urinary bladder cancer progression

Abstract

Abstract. This study evaluates the influence of the TP53 genetic status on tumour recurrence and progression with a highly effective electrophoretic technique. DNA from tissue of 75 non-invasive urinary bladder cancers was PCR amplified in the TP53 exons 5-8 and run on horizontal polyacrylamide gels under defined temperature conditions to yield specific gel shifts. Kaplan-Meier and Cox-Regression analysis were performed with tumour progression. The overall tumour recurrence in our patient population was 76.0% (57/75). Tumour recurrence frequency was 69.4% (34/49) in patients with TP53 wild-type, and 88.5% (23/26) in patients with TP53 mutation. There was no statistically significant difference with regard to recurrence frequency and time to recurrence. The progression-free survival was significantly shorter in patients with TP53 mutations, and the frequency of tumour progression was significantly higher in mutated as compared to wild-type tumours. Cox-Regression analysis showed a significant and independent influence of TP53 mutation on tumour progression in comparison with tumour grade, stage and history of prior bladder cancer. If segregated by exons, mutations in the DNA binding region of exon 8 seem to have a particular high influence on tumour progression. We conclude that genetic analysis of TP53 can select patients at high risk of bladder tumour progression that should be followed closely and may benefit from early radical surgical procedures.

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Liver, Bladder, Cervical, and Gastric Cancers

“…Some results, however, suggest that tumor protein p53 (TP53) genetic mutations may be independent prognostic factors for poor progression-free survival in noninvasive bladder cancer (343)(344)(345). Furthermore, mutations at certain sites of the TP53 gene, particularly at exon 8, may be responsible for worse prognosis because these sites involve the biological function of p53 (346 ). Mutations in defined structural and functional domains of p53 may therefore serve as useful molecular biological markers for determining prognosis and treatment strategies in patients with noninvasive transitional cell carcinomas.…”

Pterostilbene Protection and Bladder Cancer Cells

“…For instance, progression-free survival is significantly shorter in patients with a p53 mutation compared with patients with wild-type p53. 50,51 Alteration in the Rb1 pathway was commonly found in the development of invasive bladder cancer, and has been demonstrated to be significantly associated with tumor stage and tumor grade. 51,52 In addition, epigenetic aberrations were also identified in bladder cancers that p16INK4A was hypermethylation in 7 to 60% of bladder cancers.…”

“…50,51 Alteration in the Rb1 pathway was commonly found in the development of invasive bladder cancer, and has been demonstrated to be significantly associated with tumor stage and tumor grade. 51,52 In addition, epigenetic aberrations were also identified in bladder cancers that p16INK4A was hypermethylation in 7 to 60% of bladder cancers. Methylation of Cdh1 (E-cadherin) was associated with shortened survival, and methylation of lama3, lamb3, and lamc2 increased cell adhesion, differentiation, and migration.…”

Mutation Spectra of Kras and Tp53 in Urethral and Lung Neoplasms in B6C3F1 Mice Treated with 3,3′,4,4′-Tetrachloroazobenzene

“…These include cell cycle genes (Tp53, Cdk1, Rb1, and Cdkn2a), apoptosis genes (Bcl2), and signal transduction genes (Hras, Kras, Fgfr3, and Erbb2;Knowles 2001;Mitra, Bartsch, and Cote 2009). In particular, TP53 genetic mutations are independent prognostic factors for poor progression-free survival in urothelial carcinomas (Ecke et al 2008). In human pulmonary carcinomas, Kras accounts for 90% of RAS mutations, and approximately 97% of Kras mutations involve codons 12 or 13 (Forbes et al 2006).…”

“…Therefore, our primary objectives in the current study were to confirm the urothelial origin of TCAB-induced urinary tract tumors and to evaluate TCAB-induced urinary tract and pulmonary tumors for the involvement of alterations in oncogenes and tumor suppressor genes (K-ras and Tp53) important in the pathogenesis of a variety of human cancers, including lung and urinary tract neoplasia (Berggren et al 2001;Lin et al 2005;Ecke et al 2008). …”