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vesical carcinomas
Saturday 6 November 2004
bladder carcinomas, bladder cancer, bladder carcinoma
Definition: Malignant epithelial tumors of the bladder.
Bladder cancer ranks fifth in cancer incidence in the Western Hemisphere and is a leading cause of death from genitourinary cancer, with 145,000 deaths annually worldwide (mostly vesical carcinomas).
Images
invasive bladder carcinoma / cancer
Etiology
Bladder cancers are mainly caused by environmental harm, such as smoking, xposure to chemicals, such as arylamines or arsenic in drinking water, chronic irritation,e.g. caused by Schistosomiasis. Heavy exposure to Schistosomiasis may cause squamous cell carcinoma of the bladder,while currently lower levels of Schistomiasis due to preventive programs result in shift to urothelial carcinomas in endemic areas like Egypt.
There is a strong variation in incidence of bladder cancer across the world,with highest
incidences in Europe and Northern America and and lowest incidence in lndia and China.
Types (Examples)
vesical transitional cell carcinoma
vesical squamous cell carcinoma
Oncogenetics
Bladder tumors constitute a very heterogeneous disease. Superficial tumors are characterized by a high prevalence of FGFR3 mutations and chromosome 9 alterations. High-grade and muscle-invasive tumors are characterized by TP53 mutations and aneuploidy.
PIK3CA mutations
- PIK3CA mutations are an early genetic alteration associated with FGFR3 mutations in superficial papillary bladder tumors. (16885334)
The two-pathway model of bladder carcinogenesis separati ng a favourable pathway characterized by mutations in the fibroblast growth factor 3 gene (FGFR3) and a clinically unfavorable pathway characterized by genetic instability and mutations in the p53 gene is now well-established.
Non-invasive (pT1a), superficially invasive (pTl1) and muscle invasive (pT2) bladder cancers can be separated statistically on the basis of extent of genomic instability.
Expression (cDNA) array analyses are able to define mRNA signatures specifically associated the two pathways of bladder carcinogenesis. Genetie studies of flat and papillary urothelial hyperplasia on patients with an associated papillary low grade urothelial carcinoma showed frequent genetic alterations in chromosome 9, while chromosomal changes more specifically associated with aggressive bladder cancer (loss of 17p,2q, 4p) were uncommon.
ln another study on patients with urothelial hyperplasia in association with low and/or high grade urothelial carcinomas a FGFR3 gene mutation was identified in two of the four hyperplasias accompanied by low grade papillary urothelial carcinoma, providing support to the view that some lesions with the morphology of (papillary) urothelial hyperplasia in patients with bladder cancer represent a (pre-) neoplastic lesion.
Furthermore,genetic alterations (including loss of heterozygosity of chromosome 9) has frequently been observed in normal urothelium of patients with (low grade) bladder cancer. ln contrast,a very recent study failed to identify FGFR3 mutations in normal urothelium in the vicinity of a bladder cancer. These results imply that genetic alterations, such as loss of heterozygosity for chromosome 9 precede FGFR3 gene mutations in the low grade papillary carcinoma pathway of bladder carcinogenesis.
Molecular grading may become a future tool for assessment of the aggressiveness of bladder cancers.
Carcinoma in situ of the urinary bladder may be an isolated finding (primary carcinoma
in situ) or in association with almost invariably high grade papillary urothelial carcinoma, aise known as secondary carcinoma in situ.
According to the current model of carcinogenesi s carcinoma in situ may both precede high grade papillary urothelial carcinoma or it may be the sequel of papillary urothelial carcinoma.
About 80% of secondary carcinoma in situ lesions display both mutant p53 gene and chromosome 9 deletions, while FGFR3 gene mutations are very uncommon in carcinoma in situ.
References
Haynes MD, Martin TA, Jenkins SA, Kynaston HG, Matthews PN, Jiang WG. Tight junctions and bladder cancer. Int J Mol Med. 2005 Jul;16(1):3-9. PMID: 15942671
Lopez-Beltran A, Alvarez-Kindelan J,Luque RJ, Blanca A, Quintero A,Montironi R, Cheng L,Gonzalez-Campora R,Requena MJ. Loss of heterozygos ity at 9q32-33 DBCl locus) in primary non-invasive papillary urothelial neoplasm of low malignant potential and low-grade urothelial carcinoma of the bladder and their associated normal urothelium.J Pathol 2008;215(3) :263-72.
Zieger K,Dyrskjot L,Wiuf C,Jensen JL,Andersen CL,Jensen KM,Orntoft TF. Rote of activating fibroblast growth factor receptor 3 mutations in the development of bladder tumors. Clin Cancer Res 2005;11:7709-19.
Cheng L, Zhang S, Maclennan GT, Williamson SR, Lopez-Beltran A, Montironi R. Bladder cancer :translating molecular genetic insights into clinical practice.Hum Pathol. 2011Apr;42(4):455-81.
van Rhijn BW,Vis AN, van der Kwast TH, Kirkels WJ, Radvanyi F, Ooms EC, Chopin OK,B oevé ER, Jëbsis AC, Zwarthoff EC. Molecular grading of urothelial cell carcinoma with fibroblast growth factor receptor 3 and MIB-1is superior to pathology grade for the prediction of clinical outcome. J Clin Oncol. 2003 15;21(10):1912-21.
