Absence of microsatellite instability in transitional cell carcinoma of the bladder

Bonnal, Christine; Ravery, Vincent; Toublanc, Mariane; Bertrand, Guylène; Boccon-Gibod, L; Hénin, Dominique; Grandchamp, Bernard

doi:10.1016/s0090-4295(99)00399-4

Cited by 52 publications

(38 citation statements)

References 22 publications

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“…This low frequency is similar to previous reports (Gonzalez-Zulueta et al, 1993;Linnenbach et al, 1994;Li et al, 1996;Bonnal et al, 2000), and is not surprising since an increased incidence of BC is not seen in HNPCC (Watson and Lynch, 1993). Sporadic tumours with the highest proportion showing MSI-H are those found commonly in the HNPCC spectrum, for example, colon (12%), stomach (14%) and endometrial (11%) (Arzimanoglou et al, 1998).…”

Section: Introductionsupporting

confidence: 90%

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Distinct patterns of microsatellite instability are seen in tumours of the urinary tract

Catto

Azzouzi

Amira³

et al. 2003

Oncogene

123

109

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To date, two forms of microsatellite instability (MSI) have been described in human cancer. MSI typical of hereditary nonpolyposis colon cancer (HNPCC), is due to deficient DNA mismatch repair (MMR) and is defined with mono-and dinucleotide repeat microsatellites. A second variety of instability is best seen at selective tetranucleotide repeats (EMAST; elevated microsatellite alterations at select tetranucleotides). While MSI occurs infrequently in bladder cancers, EMAST is common. Sporadic tumours with the largest proportion showing MSI are those found most frequently in HNPCC kindreds. While bladder cancer is not frequently seen in HNPCC, upper urinary tract tumours (UTTs) are. Having previously found a low frequency of MSI in bladder cancer, we sought to determine the relative levels of MSI and EMAST in transitional cell carcinoma (TCC) of the upper and lower urinary tracts. Microsatellite analysis was performed at 10 mono-and dinucleotide and eight tetranucleotide loci, in 89 bladder and 71 UTT TCC. Contrasting patterns of instability were seen in urinary tumours. In bladder cancer, MSI was rare and EMAST was common. The presence of EMAST was not related to tumour grade, stage, subsequent outcome or immunohistochemical expression of the MMR proteins. In UTT, while MSI occurred frequently, EMAST was seen less frequently than in bladder cancer. When TCC of the upper and lower urinary tracts are compared, MSI-H is more frequent in UTT and EMAST more frequent in bladder cancer. Our findings show that, as for colorectal cancer, the pattern of MSI varies with location in the urinary tract. In addition, we have confirmed that MSI and EMAST are discrete forms of MSI, and that the presence of EMAST does not affect tumour phenotype.

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Section: Introductionsupporting

confidence: 90%

“…Conflicting reports of the frequency of MSI in many tumours have been published, for example, 0-100% in transitional cell carcinoma (TCC) of the bladder (Christensen et al, 1998;Bonnal et al, 2000). This variation may, in part, be due to differences in the microsatellites studied.…”

Section: Introductionmentioning

confidence: 99%

Distinct patterns of microsatellite instability are seen in tumours of the urinary tract

Catto

Azzouzi

Amira³

et al. 2003

Oncogene

123

109

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“…There is a 14-fold-increased risk of urothelial cancer of the renal pelvis and ureter in patients with HNPCC (8). Previous studies of microsatellite instability in bladder cancer have shown mutation frequencies that are generally very low (33)(34)(35). Because sporadic tumors of the renal pelvis, ureter, and bladder share the same risk factors, it is unclear why the risk of bladder cancer is not increased in patients with HNPCC.…”

Section: Discussionmentioning

confidence: 99%

Upper Tract Urothelial Carcinoma: A Clinicopathologic Study Including Microsatellite Instability Analysis

et al. 2002

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Urothelial carcinoma of the renal pelvis and ureter may develop as a manifestation of the hereditary nonpolyposis colorectal cancer syndrome that is characterized by mutations in a number of DNA mismatch repair genes and detectable as microsatellite instability. In this study, we examined microsatellite instability and the clinicopathologic features of urothelial carcinoma of the renal pelvis (n ‫؍‬ 61) and ureter (n ‫؍‬ 53) from 114 consecutive patients surgically treated from 1985-1992. Clinical data were obtained through chart review. Matched normal and tumor DNA was extracted from paraffin-embedded tissue, and a panel of six microsatellite loci was analyzed. The male-female ratio was 2.8:1 with a median age of 70 years (range, 28 to 92 y). Microsatellite analysis was successful in 67 tumors, and 21 (31.3%) patients had tumors that exhibited microsatellite instability. Patients with microsatellite-unstable tumors were significantly more likely to have additional nonurologic cancers (P ‫؍‬ .015) including colorectal carcinoma (P ‫؍‬ .001) compared with patients with tumors that did not exhibit microsatellite instability. In addition, patients with microsatellite-unstable tumors showed more colorectal cancers in their family (P ‫؍‬ .026) and were more likely to have higher grade urothelial carcinoma of the upper tract (P ‫؍‬ .028). Grade and stage, but not microsatellite status, were the strongest predictors of cancer-specific survival. This study found the highest frequency of microsatellite instability in upper urothelial tract carcinomas reported to date and highlights upper tract urothelial carcinoma as a marker of the hereditary nonpolyposis colorectal cancer syndrome in some patients. These findings reinforce the importance of obtaining cancer histories in patients with upper tract urothelial carcinoma to subsequently identify individuals with the hereditary nonpolyposis colorectal cancer syndrome and at-risk relatives for surveillance and management programs.

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“…9 Conflicting results have been reported on the frequency of microsatellite instability in bladder cancers with values ranging from 0 to 100%. [10][11][12][13][14][15][16][17] More recently, a second variety of instability has been reported that appears to be not related to DNA mismatch repair deficiency and is best seen at tetranucleotide repeats. 11 This form of instability has been termed EMAST (elevated microsatellite alterations at selected tetranucleotides) and appears to occur with high frequency (approximately 40%) in bladder cancer.…”

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confidence: 99%

Prevalence and prognostic significance of microsatellite alterations in young patients with bladder cancer

et al. 2005

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Mutations in microsatellite sequences are a hallmark of neoplastic transformation and have been reported in the majority of human cancers. Conflicting results have been reported on the role of microsatellite alterations in bladder tumorigenesis and it has been suggested that they might be mainly involved in the development of bladder cancers in young patients. In this study, DNA was extracted from laser-microdissected samples of 51 superficial papillary bladder urothelial carcinomas arising in young patients and was analyzed for the status of 19 microsatellite loci previously reported to be associated with bladder tumorigenesis. The occurrence and the pattern of microsatellite alterations, in form of loss or length variation, was evaluated and correlated with other clinicopathologic and molecular markers. The prognostic significance of these alterations was also evaluated. Loss of heterozygosity at one or more loci was detected in all 51 tumors analyzed. Length variation in at least one locus was observed in 48 (94%) of the cases. The microsatellite that was more frequently altered was D11S488 (69%), followed by D9S162 (61%), D3S3050 (55%), D3S1300 (51%) and D4S243 (51%), all the remaining being altered in less than 50% of cases. The occurrence of microsatellite alterations was not associated with tumor grade nor with tumor stage, the expression of p53, cyclin D1 or the cyclin-dependent kinase-inhibitor p27Kip1 while it was significantly more frequent in tumors with increased expression of the proliferation marker MIB-1 (P ¼ 0.003). The occurrence of alterations at the analyzed loci was associated with a reduced risk of tumor recurrence (P ¼ 0.04 by log-rank test) and disease progression (P ¼ 0.02) in a univariate analysis. These findings demonstrate that microsatellite alterations are frequent and early events and might have a prognostic significance in bladder cancers arising at young age.

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Absence of microsatellite instability in transitional cell carcinoma of the bladder

Cited by 52 publications

References 22 publications

Distinct patterns of microsatellite instability are seen in tumours of the urinary tract

Distinct patterns of microsatellite instability are seen in tumours of the urinary tract

Upper Tract Urothelial Carcinoma: A Clinicopathologic Study Including Microsatellite Instability Analysis

Prevalence and prognostic significance of microsatellite alterations in young patients with bladder cancer

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