Semiquantitative assessment of immunohistochemistry for mismatch repair proteins in Lynch syndrome.

Abstract

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<or=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<or=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.

• Authors: Emma Barrow, Emma Jagger, Judith Brierley, Andrew Wallace, Gareth Evans, James Hill, Ray McMahon
• Journal: Histopathology (Histopathology) Vol. 56 Issue 3 Pg. 331-44 (Feb 2010) ISSN: 1365-2559 [Electronic] England
• PMID: 20459533 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Biomarkers, Tumor
• DNA-Binding Proteins
• G-T mismatch-binding protein
• MLH1 protein, human
• Nuclear Proteins
• Adenosine Triphosphatases
• PMS2 protein, human
• MSH2 protein, human
• Mismatch Repair Endonuclease PMS2
• MutL Protein Homolog 1
• MutS Homolog 2 Protein
• DNA Repair Enzymes

Topics

• Adaptor Proteins, Signal Transducing (biosynthesis, genetics)
• Adenosine Triphosphatases (biosynthesis, genetics)
• Area Under Curve
• Biomarkers, Tumor (analysis)
• Colorectal Neoplasms, Hereditary Nonpolyposis (diagnosis, genetics, metabolism)
• DNA Repair Enzymes (biosynthesis, genetics)
• DNA-Binding Proteins (biosynthesis, genetics)
• Female
• Heterozygote
• Humans
• Immunohistochemistry (methods)
• Male
• Mismatch Repair Endonuclease PMS2
• MutL Protein Homolog 1
• MutS Homolog 2 Protein (biosynthesis, genetics)
• Nuclear Proteins (biosynthesis, genetics)
• ROC Curve
• Sensitivity and Specificity