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<p>Microsatellite instability (MSI), detected via immunohistochemistry and/or polymerase chain reaction (PCR), is a hallmark for Lynch syndrome and a prognostic marker in colorectal cancer. While MSI status is assessed using immunohistochemistry on archival formalin-fixed paraffin-embedded (FFPE) tissue, interpretation can be challenging due to preanalytical variability, antigen decay, and observer subjectivity. PCR-based methods, like the Idylla system, offer a rapid automated alternative with minimal hands-on time and no requirement for specialized molecular facilities. We evaluated Idylla’s performance on archival (≥ 10&#xa0;years old) FFPE colorectal cancer resections by comparing <i>BRAF</i> and MSI analysis results with immunohistochemistry for DNA mismatch repair (MMR) proteins and previously performed PCR MSI (Pentaplex) and <i>BRAF</i> genotyping assays. MSI concordance was 94.3% (50/53) between Idylla and immunohistochemistry, and 98.1% (52/53) between Idylla and PCR. Two discordant samples were classified as MSI-high by Idylla and PCR, whereas immunohistochemistry showed normal MMR expression. Conversely, the third discordant sample was classified as microsatellite stable by Idylla and PCR, while immunohistochemistry indicated deficient MMR expression. For <i>BRAF</i> genotyping, concordance between Idylla and PCR was 92.7% (38/41). In two discordant samples, <i>BRAF</i> variants identified by PCR were not included in the Idylla panel, while the third discordant sample showed a pathogenic <i>BRAF</i> variant by Idylla not confirmed by PCR. This is the largest study evaluating Idylla on archival FFPE material. High concordance with traditional methods suggests that Idylla can be used as an alternative approach for Lynch syndrome screening, improving accessibility and reliability of MSI and <i>BRAF</i> testing in challenging archival specimens.</p>

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Validation of Idylla MSI and BRAF genotype tests on archival colorectal cancer samples for retrospective Lynch syndrome detection

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月16日

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  • Margarita Melnikova Jørgensen,
  • Ida Elisabeth Gad Holm,
  • Claus Lindbjerg Andersen,
  • Jesper Bertram Bramsen,
  • Parag Deepak Dabir

摘要

Microsatellite instability (MSI), detected via immunohistochemistry and/or polymerase chain reaction (PCR), is a hallmark for Lynch syndrome and a prognostic marker in colorectal cancer. While MSI status is assessed using immunohistochemistry on archival formalin-fixed paraffin-embedded (FFPE) tissue, interpretation can be challenging due to preanalytical variability, antigen decay, and observer subjectivity. PCR-based methods, like the Idylla system, offer a rapid automated alternative with minimal hands-on time and no requirement for specialized molecular facilities. We evaluated Idylla’s performance on archival (≥ 10 years old) FFPE colorectal cancer resections by comparing BRAF and MSI analysis results with immunohistochemistry for DNA mismatch repair (MMR) proteins and previously performed PCR MSI (Pentaplex) and BRAF genotyping assays. MSI concordance was 94.3% (50/53) between Idylla and immunohistochemistry, and 98.1% (52/53) between Idylla and PCR. Two discordant samples were classified as MSI-high by Idylla and PCR, whereas immunohistochemistry showed normal MMR expression. Conversely, the third discordant sample was classified as microsatellite stable by Idylla and PCR, while immunohistochemistry indicated deficient MMR expression. For BRAF genotyping, concordance between Idylla and PCR was 92.7% (38/41). In two discordant samples, BRAF variants identified by PCR were not included in the Idylla panel, while the third discordant sample showed a pathogenic BRAF variant by Idylla not confirmed by PCR. This is the largest study evaluating Idylla on archival FFPE material. High concordance with traditional methods suggests that Idylla can be used as an alternative approach for Lynch syndrome screening, improving accessibility and reliability of MSI and BRAF testing in challenging archival specimens.