RGD Reference Report - Prognostic value of microsatellite instability determined by immunohistochemical staining of hMSH2 and hMSH6 in urothelial carcinoma of the bladder. - Rat Genome Database

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Prognostic value of microsatellite instability determined by immunohistochemical staining of hMSH2 and hMSH6 in urothelial carcinoma of the bladder.

Authors: Mylona, E  Zarogiannos, A  Nomikos, A  Giannopoulou, I  Nikolaou, I  Zervas, A  Nakopoulou, L 
Citation: Mylona E, etal., APMIS. 2008 Jan;116(1):59-65.
RGD ID: 2293503
Pubmed: PMID:18254781   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1600-0463.2008.00760.x   (Journal Full-text)

Mismatch repair (MMR) genes are involved in the recognition and repair of acquired DNA damage, which arises during cell division, thus playing an essential role in preserving genetic stability. Immunohistochemistry was applied to 130 specimens from urothelial carcinoma (UC) of the bladder to detect expression of MMR gene products hMSH2 and hMSH6, and to investigate its clinicopathological and prognostic value. hMSH2 and hMSH6 protein expression was exclusively detected in the nuclei of malignant cells. Of the 112 cases evaluable for hMSH2, 29 (25.9%) were negative and of the 130 UCs evaluable for hMSH6, 64 (49.2%) were negative, and were thus considered to depict MSI. Nuclear hMSH2 values were statistically lower in non-invasive UCs (Ta-T1) (p=0.013) and in carcinomas with decreased p53 staining (p=0.04). Lower hMSH6 values were more often met in well-differentiated tumors (p<0.0001) and in tumors with low expression of p53 (p=0.016), topoIIalpha and caspase 3 (p=0.017 and p=0.018, respectively). Both hMSH2- and hMSH6-negative immunoreactions were found to have a favorable impact on overall patient survival (p=0.041 and p=0.034, respectively), this finding being further verified in the multivariate analysis of hMSH2 (p=0.026). This is the first study to show that lack (and not reduction designated according to various cut-off points) of hMSH2 and hMSH6 correlated with non-invasive tumors of lower grade and is of favorable prognostic significance in patients suffering from bladder carcinoma.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MSH2Humanurinary bladder cancer disease_progressionIEP protein:decreased expression:urinary bladderRGD 
MSH6Humanurinary bladder cancer disease_progressionIEP protein:decreased expression:urinary bladderRGD 
Msh2Raturinary bladder cancer disease_progressionISOMSH2 (Homo sapiens)protein:decreased expression:urinary bladderRGD 
Msh2Mouseurinary bladder cancer disease_progressionISOMSH2 (Homo sapiens)protein:decreased expression:urinary bladderRGD 
Msh6Mouseurinary bladder cancer disease_progressionISOMSH6 (Homo sapiens)protein:decreased expression:urinary bladderRGD 

Objects Annotated

Genes (Rattus norvegicus)
Msh2  (mutS homolog 2)

Genes (Mus musculus)
Msh2  (mutS homolog 2)
Msh6  (mutS homolog 6)

Genes (Homo sapiens)
MSH2  (mutS homolog 2)
MSH6  (mutS homolog 6)


Additional Information