Molecular biology of bladder cancer

Abstract

Bladder cancer is a major cause of health expenses and it presents formidable clinical challenges. Two types of tumors have been identified, papillary and non-papillary. The former are mainly characterized by FGFR3 and chromosome 9 alterations and a low frequency of Tp53 alterations. The latter are characterized by a high frequency of alterations in genes in the p53 and Rb pathways. Chromosome 9 alterations, specially in 9q, are crucial to bladder cancer development and occur in both types of tumors. Progression of some superficial tumors (mainly TaG3 and T1G3) to high-grade, invasive, carcinomas provides evidence of some overlap between the two pathways. Distinct gene expression profiles have been identified in superficial and invasive tumors. The stage is now ready for the clinical application of this knowledge.

A study of p53 expression in transitional cell carcinoma of urinary bladder in Erbil

“…Group 4 in which p53 expression was >50%, was the most common group in both age groups (<60 and ≥60) years, comprising 22 (75.9%) and 48 (67.6%) of cases respectively as Table (3).There was no significant correlation between ages of patient with p53 expression in TCC. (x²=2.428, p=0.488).The correlation of p53 expression with the gender of cases of TCC is shown in Table (3).The p53 expression was higher in group 4 (>50%) in most of the cases for male patients as well as female patients comprising 66.6% and 81.8% respectively .There was no statistically significant correlation between gender of patient and p53 expression in transitional cell carcinoma of urinary bladder (x²=2.214, p=0.529).The correlation of p53 expression with histological architecture of TCC of urinary bladder is shown in Table ( 4).Group4 in which p53 expression was >50%, solid histological architecture showed higher p53 expression (78.6%) than papillary type (63.8%).There was a statistically significant correlation between p53 expression and histological architecture of cases of TCC (X²=9.494, P=0.023).The correlation of p53 expression with grading of TCC of urinary bladder is shown in Table ( Urinary bladder cancer is a common disease worldwide. The incidence of UB cancer varies over the world with the highest rates in developed communities.…”

“…Papillary lesions are the most common and usually arise in hyperplastic urothelium whereas invasive tumors arise from dysplastic urothelium. 4 Classically bladder cancer has been associated with exogenous and environmental risk factors. The two best known risk factors for bladder cancer are smoking and occupational exposure.…”

Anatomical Location of Urothelial Carcinomas of the Urinary Tract Leads To Perspectives of Specific Treatment

“…The analysis of p53 gene mutations and of the pattern of genetic changes has also established the clonal nature of synchronous urothelial tumors in most urinary tract cancers [9,10]. Heterogeneity or oligoclonality could be explained by clonal divergence and the selection of different cell populations originating from an initial common tumor cell.…”

“…Studies of the genetic changes that occur during the onset and development of urothelial carcinomas have characterized the specific chromosomes involved and have established a sequence of events. Some of the changes occur in superficial tumors and are associated with tumor onset; others are specific to infiltrating or high-grade tumors and are involved in tumor progression [9,10]. The proposed schemes for the sequence of genetic events are neither exhaustive nor identical, but all agree that the tumor develops in several stages, each of which is associated with specific genetic changes [11].…”

“…In fact, there would appear to be two pathways of carcinogenesis, one leading to superficial tumors, the other to highgrade tumors. The key change in the genesis of high-grade tumors would be loss of function of the p53 gene on chromosome 17p [10,12]. With the exception of tumor clonality, little is known about the molecular events underlying urothelial carcinomas.…”