Prognostic significance of survivin, β-catenin and p53 expression in urothelial carcinoma

Abstract

Survivin, β-catenin, and p53 are well-known cell-cycle and apoptosis regulators of tumorigenesis. Urothelial carcinomas (UCs) are the most common of the human cancers. Compared to superficial tumors (Ta, CIS, or T1), invasive UCs are important with regard to recurrence, progression, and mortality. Therefore, we examined whether survivin, β-catenin, and p53 could be used as the biomarkers for the early prediction of the invasiveness of UCs and the overall survival of the patients. We investigated the prognostic expressions of those biomarkers in UC (n=147) and in non-muscle invasive UC (NMI-UC) (n=113), using tissue microarray and immunohistochemistry. Spearman's correlation analysis and multivariate Cox regression analyses were used for statistical interpretation. High expressions of β-catenin, survivin, and p53 were associated with a high T stage, recurrence, progression, mortality, low recurrence-free survival, low progression-free survival and low overall survival (p <0.01). Similar findings were achieved for recurrence and progression in the NMI-UC group, except for mortality. Moreover, a positive correlation was shown between p53 and β-catenin and between p53 and survivin (r=0.221, p <0.01; r=0.236, p <0.01, respectively). Survivin, p53, and β-catenin overexpression, as prognostic markers, might suggest that the UCs are biologically aggressive with the poor prognosis. Thus, dysregulation of those these cell-cycle and apoptosis regulators in bladder carcinoma could be used as a molecular marker to determine the best treatment strategy and could contribute to the development of targeted therapies.

Downregulation of RNF128 Predicts Progression and Poor Prognosis in Patients with Urothelial Carcinoma of the Upper Tract and Urinary Bladder

“…TP53 mutations result in a series of downstream effects, including decreased expression of p21 12, 20-22. TP53 mutations in UC are also related to higher tumor grade, advanced stage, and worse disease outcomes 21-22. Downregulated expression of RNF128 was found to be involved in p53-induced apoptosis, playing an essential role in determining the cell fate, by Chen et al 12.…”

“…Alterations of the TP53 tumor suppressor gene play a central role in the carcinogenesis of many tumors, including UC 20-22. The TP53 gene, located on the short arm of chromosome 17 (17p13.1), encodes a 393 amino acid protein (p53) that regulates the cell cycle, DNA repair, and apoptosis 21.…”

“…The TP53 gene, located on the short arm of chromosome 17 (17p13.1), encodes a 393 amino acid protein (p53) that regulates the cell cycle, DNA repair, and apoptosis 21. TP53 mutations result in a series of downstream effects, including decreased expression of p21 12, 20-22. TP53 mutations in UC are also related to higher tumor grade, advanced stage, and worse disease outcomes 21-22.…”

“…TP53, the most frequently mutated gene, has been identified in approximately 50% of all human cancers 15-19. Moreover, p53 is one of the most commonly studied markers in UC 20-22.…”

Significance of survivin (BIRC5) as a biomarker for the assessmet of preoperative cardiovascular risk in non-cardiac surgeries: Survivin (BIRC5) as a novel cardiac biomarker

“…Svakako, i učešće u procesu angiogeneze ga čini adekvatnim tumorskim biomarkerom 40 . Različite studije su dokazale značaj survivina u: superficijalnom tumoru mokraćne bešike, tumoru želuca, tumorima ovarijuma, "non-small cell" tumoru pluća, urotelijanom tumoru, akutne i hronične limfoblastne leukemije, itd 14,39,[41][42][43][44][45][46][47] .…”