Semiquantitative assessment of immunohistochemistry for mismatch repair proteins in Lynch syndrome

Raymond Mcmahon, Emma Barrow, Emma Jagger, Judith Brierley, Andrew Wallace, Gareth Evans, James Hill, Ray McMahon

    Research output: Contribution to journalArticlepeer-review


    Aims: To assess semiquantitative immunohistochemistry as used in the diagnosis of Lynch syndrome. Methods and Results: Tumour sections from 51 mutation carriers and 17 controls were stained with antibodies against MLH1, MSH2, MSH6 and PMS2. Intensity of immunoreactivity and percentage positivity were recorded on scales of 0-3 and 0-4, respectively. These scores were multiplied for a score of 0-12 per slide. Receiver-operator characteristic (ROC) curves of staining performance for the identification of mutation carriers were evaluated, and optimum cut-offs calculated. The area under the MLH1 ROC curve was 0.981 [95% confidence interval (CI) 0.952, 1.000]. The area under the MSH2 ROC curve was 0.899 (95% CI 0.796, 1.000). For MLH1 staining, a score ≤4 gives a sensitivity of 100.0% (95% CI 84.0, 100.0) and a specificity of 91.5% (95% CI 79.6, 97.6) for identifying MLH1 mutation carriers. For MSH2 staining, a score ≤4 gives a sensitivity of 87.5% (95% CI 61.7, 98.4) and specificity of 88.5% (95% CI 76.5, 95.6) for identifying MSH2 mutation carriers. Conclusions: This study supports a semiquantitative slide assessment method. Protein expression may occur in the context of known pathogenic mutations, a potential pitfall in the screening process. © 2010 Blackwell Publishing Limited.
    Original languageEnglish
    Pages (from-to)331-344
    Number of pages13
    Issue number3
    Publication statusPublished - Feb 2010


    • Biological markers
    • DNA mismatch repair
    • Evaluation studies
    • Hereditary non-polyposis colorectal cancer
    • Immunohistochemistry
    • Lynch syndrome


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