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dc.contributor.authorKassem, Heba Sen
dc.contributor.authorVarley, Jenniferen
dc.contributor.authorHamam, S Men
dc.contributor.authorMargison, Geoffrey Pen
dc.date.accessioned2009-11-06T16:49:00Z
dc.date.available2009-11-06T16:49:00Z
dc.date.issued2001-02-02
dc.identifier.citationImmunohistochemical analysis of expression and allelotype of mismatch repair genes (hMLH1 and hMSH2) in bladder cancer. 2001, 84 (3):321-8 Br. J. Canceren
dc.identifier.issn0007-0920
dc.identifier.pmid11161395
dc.identifier.doi10.1054/bjoc.2000.1595
dc.identifier.urihttp://hdl.handle.net/10541/85606
dc.description.abstractMutation of human homologues of DNA mismatch repair (MMR) genes in tumours has been shown to be associated with the phenomenon of microsatellite instability (MSI). Several studies have reported the occurrence of MSI in bladder cancer, but evidence of involvement of MMR genes in the pathogenesis of this cancer is still unclear. We therefore utilized quantitative immunohistochemical (IHC) image analysis and PCR-based allelotype analysis to determine hMLH1 and hMSH2 genes alteration in a cohort of Egyptian bladder cancer samples. IHC analysis of 24 TCC and 12 SCC revealed marked- intra and intertumour heterogeneity in the levels of expression of the two MMR proteins. One TCC lost MLH1 expression and one lost MSH2, (1/24, 4%), and one SCC lost MSH2 (1/12, 8%). A large proportion of analysed tumours revealed a percentage positivity of less than 50% for MLH1 and MSH2 expression (44% and 69%, respectively). Complete loss of heterozygosity in three dinucleotide repeats lying within, or in close proximity to, hMLH1 and hMSH2 was rare (2/57, (4%) for MLH1; and 1/55, (2%) for MSH2), however allelic imbalance was detected in 11/57 (hMLH1) and 10/55 (hMSH2) at any of the informative microsatellite loci. These alterations in structure and expression of DNA MMR genes suggest their possible involvement in the tumorigenesis and/or progression of bladder cancer.
dc.language.isoenen
dc.subjectCancer DNAen
dc.subjectCancerous Gene Expression Regulationen
dc.subjectCancer Proteinsen
dc.subjectUrinary Bladder Canceren
dc.subject.meshAdaptor Proteins, Signal Transducing
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAlleles
dc.subject.meshAllelic Imbalance
dc.subject.meshCarrier Proteins
dc.subject.meshDNA, Neoplasm
dc.subject.meshDNA-Binding Proteins
dc.subject.meshFemale
dc.subject.meshGene Expression Regulation, Neoplastic
dc.subject.meshHumans
dc.subject.meshImmunohistochemistry
dc.subject.meshLoss of Heterozygosity
dc.subject.meshMale
dc.subject.meshMicrosatellite Repeats
dc.subject.meshMiddle Aged
dc.subject.meshMutS Homolog 2 Protein
dc.subject.meshNeoplasm Proteins
dc.subject.meshNuclear Proteins
dc.subject.meshPolymerase Chain Reaction
dc.subject.meshProto-Oncogene Proteins
dc.subject.meshUrinary Bladder Neoplasms
dc.titleImmunohistochemical analysis of expression and allelotype of mismatch repair genes (hMLH1 and hMSH2) in bladder cancer.en
dc.typeArticleen
dc.contributor.departmentCRC Carcinogenesis Group, UK.en
dc.identifier.journalBritish Journal of Canceren
html.description.abstractMutation of human homologues of DNA mismatch repair (MMR) genes in tumours has been shown to be associated with the phenomenon of microsatellite instability (MSI). Several studies have reported the occurrence of MSI in bladder cancer, but evidence of involvement of MMR genes in the pathogenesis of this cancer is still unclear. We therefore utilized quantitative immunohistochemical (IHC) image analysis and PCR-based allelotype analysis to determine hMLH1 and hMSH2 genes alteration in a cohort of Egyptian bladder cancer samples. IHC analysis of 24 TCC and 12 SCC revealed marked- intra and intertumour heterogeneity in the levels of expression of the two MMR proteins. One TCC lost MLH1 expression and one lost MSH2, (1/24, 4%), and one SCC lost MSH2 (1/12, 8%). A large proportion of analysed tumours revealed a percentage positivity of less than 50% for MLH1 and MSH2 expression (44% and 69%, respectively). Complete loss of heterozygosity in three dinucleotide repeats lying within, or in close proximity to, hMLH1 and hMSH2 was rare (2/57, (4%) for MLH1; and 1/55, (2%) for MSH2), however allelic imbalance was detected in 11/57 (hMLH1) and 10/55 (hMSH2) at any of the informative microsatellite loci. These alterations in structure and expression of DNA MMR genes suggest their possible involvement in the tumorigenesis and/or progression of bladder cancer.


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