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Article

Mismatch repair hMSH2, hMLH1, hMSH6 and hPMS2 mRNA expression profiles in precancerous and cancerous urothelium

  • Authors:
    • Dimitra P. Vageli
    • Stavros Giannopoulos
    • Sotirios G. Doukas
    • Christos Kalaitzis
    • Stilianos Giannakopoulos
    • Alexandra Giatromanolaki
    • George K. Koukoulis
    • Stavros Touloupidis
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Medical School, University of Thessaly, Larissa, Thessaly 41110, Greece, Department of Urology, Medical School, Democritus University of Thrace and University Hospital of Alexandroupolis, Alexandroupolis 68100, Greece, Department of Pathology, Medical School, Democritus University of Thrace and University Hospital of Alexandroupolis, Alexandroupolis 68100, Greece
  • Pages: 283-294
    |
    Published online on: October 19, 2012
       https://doi.org/10.3892/ol.2012.979
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Abstract

Changes in the expression of the mismatch repair (MMR) genes hMSH2, hMLH1, hMSH6 and hPMS2 reflect dysfunction of the DNA repair system that may allow the malignant transformation of tissue cells. The aim of the present study was to address the mRNA expression profiles of the mismatch DNA repair system in cancerous and precancerous urothelium. This is the first study to quantify MMR mRNA expression by applying quantitative real-time PCR (qPCR) and translate the results to mRNA phenotypic profiles (r, reduced; R, regular or elevated) in bladder tumors [24 urothelial cell carcinomas (UCCs) and 1 papillary urothelial neoplasm of low malignant potential (PUNLMP)] paired with their adjacent normal tissues (ANTs). Genetic instability analysis was applied at polymorphic sites distal or close to the hMSH2 and hMLH1 locus. Presenting our data, reduced hMSH2, hMSH6 and hPMS2 mRNA expression profiles were observed in cancerous and precancerous urothelia. Significantly, the ANTs of UCCs revealed the highest percentages of reduced hMSH2 (r2), hMSH6 (r6) and hPMS2 (p2) mRNA phenotypes relative to their tumors (P<0.03). In particular, combined r2r6 (P<0.02) presented a greater difference between ANTs of low‑grade UCCs vs. their tumors compared with ANTs of high‑grade UCCs (P=0.000). Reduced hMLH1 (r1) phenotype was not expressed in precancerous or cancerous urothelia. The hMSH6 mRNA was the most changed in UCCs (47.8%), while hMSH2, hMLH1 and hPMS2 showed overexpression (47.8, 35 and 30%, respectively) that was associated with gender and histological tumor grading or staging. Genetic instability was rare in polymorphic regions distal to hMLH1. Our data reveal a previously unrecognized hMSH2 and hMSH6 mRNA combined phenotype (r2r6) correlated with a precancerous urothelium and show that hMLH1 is transcriptionally activated in precancerous or cancerous urothelium. In the present study, it is demonstrated that reduction of hMSH6 mRNA is a frequent event in bladder tumorigenesis and reflects a common mechanism of suppression with hMSH2, while alterations of hMSH2 or hMLH1 mRNA expression in UCCs does not correlate with the allelic imbalance of polymorphic regions harboring the genes.
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Copy and paste a formatted citation
Spandidos Publications style
Vageli DP, Giannopoulos S, Doukas SG, Kalaitzis C, Giannakopoulos S, Giatromanolaki A, Koukoulis GK and Touloupidis S: Mismatch repair hMSH2, hMLH1, hMSH6 and hPMS2 mRNA expression profiles in precancerous and cancerous urothelium. Oncol Lett 5: 283-294, 2013.
APA
Vageli, D.P., Giannopoulos, S., Doukas, S.G., Kalaitzis, C., Giannakopoulos, S., Giatromanolaki, A. ... Touloupidis, S. (2013). Mismatch repair hMSH2, hMLH1, hMSH6 and hPMS2 mRNA expression profiles in precancerous and cancerous urothelium. Oncology Letters, 5, 283-294. https://doi.org/10.3892/ol.2012.979
MLA
Vageli, D. P., Giannopoulos, S., Doukas, S. G., Kalaitzis, C., Giannakopoulos, S., Giatromanolaki, A., Koukoulis, G. K., Touloupidis, S."Mismatch repair hMSH2, hMLH1, hMSH6 and hPMS2 mRNA expression profiles in precancerous and cancerous urothelium". Oncology Letters 5.1 (2013): 283-294.
Chicago
Vageli, D. P., Giannopoulos, S., Doukas, S. G., Kalaitzis, C., Giannakopoulos, S., Giatromanolaki, A., Koukoulis, G. K., Touloupidis, S."Mismatch repair hMSH2, hMLH1, hMSH6 and hPMS2 mRNA expression profiles in precancerous and cancerous urothelium". Oncology Letters 5, no. 1 (2013): 283-294. https://doi.org/10.3892/ol.2012.979
Copy and paste a formatted citation
x
Spandidos Publications style
Vageli DP, Giannopoulos S, Doukas SG, Kalaitzis C, Giannakopoulos S, Giatromanolaki A, Koukoulis GK and Touloupidis S: Mismatch repair hMSH2, hMLH1, hMSH6 and hPMS2 mRNA expression profiles in precancerous and cancerous urothelium. Oncol Lett 5: 283-294, 2013.
APA
Vageli, D.P., Giannopoulos, S., Doukas, S.G., Kalaitzis, C., Giannakopoulos, S., Giatromanolaki, A. ... Touloupidis, S. (2013). Mismatch repair hMSH2, hMLH1, hMSH6 and hPMS2 mRNA expression profiles in precancerous and cancerous urothelium. Oncology Letters, 5, 283-294. https://doi.org/10.3892/ol.2012.979
MLA
Vageli, D. P., Giannopoulos, S., Doukas, S. G., Kalaitzis, C., Giannakopoulos, S., Giatromanolaki, A., Koukoulis, G. K., Touloupidis, S."Mismatch repair hMSH2, hMLH1, hMSH6 and hPMS2 mRNA expression profiles in precancerous and cancerous urothelium". Oncology Letters 5.1 (2013): 283-294.
Chicago
Vageli, D. P., Giannopoulos, S., Doukas, S. G., Kalaitzis, C., Giannakopoulos, S., Giatromanolaki, A., Koukoulis, G. K., Touloupidis, S."Mismatch repair hMSH2, hMLH1, hMSH6 and hPMS2 mRNA expression profiles in precancerous and cancerous urothelium". Oncology Letters 5, no. 1 (2013): 283-294. https://doi.org/10.3892/ol.2012.979
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