p53 status correlates with the differential expression of the DNA mismatch repair protein MSH2 in non-small cell lung carcinoma

Authors

  • George Xinarianos,

    1. Molecular Oncology Unit, Roy Castle International Centre for Lung Cancer Research, Liverpool, United Kingdom
    2. Molecular Genetics and Oncology Group, Department of Clinical Dental Sciences, University of Liverpool, Liverpool, United Kingdom
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  • Triantafillos Liloglou,

    1. Molecular Oncology Unit, Roy Castle International Centre for Lung Cancer Research, Liverpool, United Kingdom
    2. Molecular Genetics and Oncology Group, Department of Clinical Dental Sciences, University of Liverpool, Liverpool, United Kingdom
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  • Wendy Prime,

    1. Molecular Oncology Unit, Roy Castle International Centre for Lung Cancer Research, Liverpool, United Kingdom
    2. Department of Pathology, Medical School, University of Liverpool, Liverpool, United Kingdom
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  • George Sourvinos,

    1. Laboratory of Virology, Medical School, University of Crete, Heraklion, Crete, Greece
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  • Andreas Karachristos,

    1. Laboratory of Virology, Medical School, University of Crete, Heraklion, Crete, Greece
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  • John R. Gosney,

    1. Department of Pathology, Medical School, University of Liverpool, Liverpool, United Kingdom
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  • Demetrios A. Spandidos,

    1. Laboratory of Virology, Medical School, University of Crete, Heraklion, Crete, Greece
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  • John K. Field

    Corresponding author
    1. Molecular Oncology Unit, Roy Castle International Centre for Lung Cancer Research, Liverpool, United Kingdom
    2. Molecular Genetics and Oncology Group, Department of Clinical Dental Sciences, University of Liverpool, Liverpool, United Kingdom
    • Roy Castle International Centre for Lung Cancer Research, 200 London Road, Liverpool, Merseyside L3 9TA, UK
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    • Fax: +44-151-794 8989


Abstract

We examined the p53 status of 108 NSCLCs compared to the expression of MLH1 and MSH2 proteins. p53 overexpression was demonstrated by IHC in 64% of patients examined, whereas p53 mutations were detected in 43%. Twenty-two percent of mutations were located outside of the hot-spot (exons 5–8) area. p53 mutations and overexpression were more frequent in SCCL (57% and 73%, respectively) than in lung adenocarcinomas (22% and 50%, respectively). In NSCLC-carrying wild-type p53, increased expression of MSH2 correlated with p53 overexpression (p = 0.018). In addition, in SCCL, p53 mutations correlated with reduced MSH2 expression (p = 0.019). These data suggest a relationship between p53 and MSH2. While there is evidence for p53 being a transcriptional activator of MSH2, the hypothesis that MSH2 acts as a DNA-damage signaller triggering p53 overexpression needs to be clarified in future studies. © 2002 Wiley-Liss, Inc.

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