Loss of heterozygosity on chromosomes 11 and 17 are markers of recurrence in TCC of the bladder

Edwards, Joanne; Duncan, Pamela; Going, James J.; Grigor, Ken; Watters, A.D.; Bartlett, John M.S.

doi:10.1054/bjoc.2001.2159

Cited by 20 publications

(13 citation statements)

References 36 publications

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“…Previously, research from this laboratory has shown an observed increase in aneusomy from pTa to pT1 TCCs, but a lack of association with stage and recurrence or progression, suggesting that it is aneusomy and not pathological classification which is driving progression in pTa or pT1 tumours (Watters et al, , 2002Edwards et al, 2001). Furthermore, it is of interest to note that the rate of genetic abnormalities is similar when comparing the data from patients who progress from nonmuscle-invasion and those who present with muscle invasion.…”

Section: Discussionmentioning

confidence: 98%

Genetic aberrations of c-myc and CCND1 in the development of invasive bladder cancer

et al. 2002

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Detrusor muscle invasive transitional cell carcinoma is associated with poor prognosis and is responsible for the majority of bladder cancer related deaths. Amplifications of c-myc and CCND1 are associated with detrusor-muscle-invasive transitional cell carcinoma, however, their precise role in driving disease progression is unclear. Fluorescence in situ hybridisation on archival tissue from 16 patients with primary diagnosis of 5pT2 transitional cell carcinoma and 15 cases with primary pTa/pT1 disease subsequently progressing to detrusor-muscle-invasion was performed, in the latter group both pre and post muscle invasive events were studied. No patients presenting with 5pT2 had amplification of c-myc, two out of 16 (12.5%) had CCND1 amplification. Of patients who developed 5pT2, two out of 15 (13.3%) had amplification of c-myc, both in 5pT2, five out of 15 (33.3%) had CCND1 amplification, two in pTa/pT1 tumours, three in 5pT2 transitional cell carcinomas. In total, two out of 31 (6.5%) of patients' 5pT2 TCCs were amplified for c-myc and six out of 31 (19%) were amplified for CCND1. Eighty-seven per cent (40 out of 46) of tumours were polysomic for chromosome 8 and 80% (37 out of 46) were polysomic for chromosome 11 and this reflected the high copy numbers of c-myc and CCND1 observed. In almost all cases an increase in c-myc/CCND1 copy number occurred prior to invasion and persisted in advanced disease. Amplification of CCND1 or alterations in c-myc/CCND1 early in bladder cancer may have clinical relevance in promoting and predicting progression to detrusor-muscle-invasive transitional cell carcinoma.

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Section: Discussionmentioning

confidence: 98%

Genetic aberrations of c-myc and CCND1 in the development of invasive bladder cancer

et al. 2002

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“…HER2/neu has been studied in TCC with the aim to evaluate the potential for molecular targeted therapy. 24 Gene amplification and protein overexpression were first described in bladder carcinoma by Zhau et al 25 29,30 It was noted that another important element related to progression of bladder cancer is the presence of numerical alterations of some chromosomes [14][15][16][17][18] and in particular, aberrations affecting chromosome 17 16,17,22 as polysomy. 19,20,28 It has been found that polysomy of chromosome 17 is involved in the progression to detrusor-muscle invasion and has been associated with aggressive tumor behavior and recurrence of disease.…”

Section: Discussionmentioning

confidence: 99%

Role of Polysomy 17 in Transitional Cell Carcinoma of the Bladder: Immunohistochemical Study of HER2/neu Expression and FISH Analysis of c-erbB-2 Gene and Chromosome 17

et al. 2009

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This study investigates the potential clinical significance of c-erbB-2 gene and chromosome 17 alterations by fluorescence in situ hybridization (FISH) analysis and HER2/neu overexpression by immunohistochemical staining in transitional cell carcinoma (TCC) of urinary bladder correlating the results with tumor stage and grade categories and with clinical behavior. Sixty-three cases of TCC retrieved from the files of 2 institutions were analyzed for chromosome 17 aberrations and c-erbB-2 amplification by FISH analysis and evaluated immunohistochemically for HER2/neu overexpression. Five tumors were G1, 29 intermediate grade (G2), and 29 tumors high grade (G3); 32 tumors had stage Ta, 18 tumors T1, and 13 tumors T2. We found polysomy of chromosome 17 in 58.7% of TCC with average chromosome copy number >2.26; increased number of HER2/neu gene copy was observed in 66.7% of tumors. C-erbB-2 amplification occurred in 6.3% of tumors. Immunohistochemically, 60.3% of TCC overexpressed HER2/neu and 39.7% of tumors were negative. All tumors with polysomy showed simultaneously increase of HER2/neu gene copy number of which 34/37 with protein overexpression. A statistically significant correlation between polysomy of chromosome 17 and tumor stage (P = .0003) and tumor grade (P < .0001) was found; polysomy was not seen in G1 tumors; however, 8/29 G2 tumors and 29/29 G3 tumors revealed polysomy of chromosome 17; in 8/32 Ta tumors, 14/18 T1 and 13/13 of deeply invasive tumors (T2) polysomy 17 was observed. Moreover, it was found that 7 superficial tumors (1 Ta and 6 T1) showed high polysomy with average of chromosome 17 copy number > or =3.76 as observed in all invasive tumors. The data suggest that although HER2/neu amplification, found in high grade and invasive tumors, is a rare event in TCC, polysomy of chromosome 17 is an important factor correlated with tumor stage and grade categories and could be considered a molecular marker of tumor progression with interesting diagnostic implications.

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“…A global analysis may provide information of whole-genome alterations in gene copy number. LOHs at some microsatellite loci have been shown to be significantly associated with clinical outcomes [39][40][41][42][43][44], including tumor recurrence-free survival [42,43] and progression-free survival [43].…”

Section: Structural Chromosomal Alterationsmentioning

confidence: 99%

Bladder cancer: translating molecular genetic insights into clinical practice

Liu¹,

Zhang²,

MacLennan³

et al. 2011

Human Pathology

168

124

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Loss of heterozygosity on chromosomes 11 and 17 are markers of recurrence in TCC of the bladder

Cited by 20 publications

References 36 publications

Genetic aberrations of c-myc and CCND1 in the development of invasive bladder cancer

Genetic aberrations of c-myc and CCND1 in the development of invasive bladder cancer

Role of Polysomy 17 in Transitional Cell Carcinoma of the Bladder: Immunohistochemical Study of HER2/neu Expression and FISH Analysis of c-erbB-2 Gene and Chromosome 17

Bladder cancer: translating molecular genetic insights into clinical practice

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