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Screening for Muir-Torre Syndrome Using Mismatch Repair Protein Immunohistochemistry of Sebaceous Neoplasms

  • Original Research
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Journal of Genetic Counseling

Abstract

Screening for the Muir-Torre variant of Lynch Syndrome (LS) using Mismatch Repair (MMR) gene immunohistochemistry (IHC) on sebaceous neoplasms (SNs) is technically feasible. To date, research into the clinical utility of MMR IHC for this indication is limited. We conducted a retrospective chart review of 90 patients with MMR IHC completed on at least one SN from January 2005 to May 2010. SNs included were adenomas, epitheliomas, carcinomas and basal and squamous cell carcinomas with sebaceous differentiation. Of the 90 patients, 13 (14 %) had genetically confirmed or fulfilled clinical criteria for a diagnosis of MTS and 51 patients (57 %) presented with an abnormal MMR IHC result (loss of one or more MMR proteins) on at least one SN. Abnormal IHC had a sensitivity of 85 %, specificity of 48 %, positive predictive value (PPV) of 22 % and negative predictive value (NPV) of 95 % when evaluating for MTS. When personal or family history of colorectal cancer (≥2 family members with a history of colorectal cancer) was taken into consideration, ignoring IHC results, sensitivity was 92 %, specificity was 99 %, PPV was 92 % and NPV was 99 %. MMR IHC on SNs when used to screen for MTS has poor diagnostic utility. We recommend that MMR IHC not be performed routinely on SNs when the patient does not have either personal or family history of colorectal cancer.

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Funding

A Mayo Clinic Clinical Translational Science Grant.

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Authors and Affiliations

  1. Mayo Clinic, Medical Genetics, 4500 San Pablo Road, Jacksonville, FL, 32224, USA

    Maegan E. Roberts & Douglas L. Riegert-Johnson

  2. Mayo Clinic, Gastroenterology, Jacksonville, FL, USA

    Douglas L. Riegert-Johnson

  3. Mayo Clinic, Laboratory Medicine and Pathology, Rochester, MN, USA

    Brittany C. Thomas & Kandelaria M. Rumilla

  4. Mayo Clinic, Biostatistics, Jacksonville, FL, USA

    Colleen S. Thomas & Michael G Heckman

  5. Mayo Clinic, Pathology, Jacksonville, FL, USA

    Murli Krishna

  6. Mayo Clinic, Dermatology, Scottsdale, AZ, USA

    David J. DiCaudo

  7. Mayo Clinic, Dermatology, Rochester, MN, USA

    Alina G Bridges

  8. Mayo Clinic, Medical Genetics, Scottsdale, AZ, USA

    Katherine S. Hunt

  9. Mayo Clinic, Dermatology, Jacksonville, FL, USA

    Mark A Cappel

Authors
  1. Maegan E. Roberts
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  2. Douglas L. Riegert-Johnson
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  3. Brittany C. Thomas
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  4. Colleen S. Thomas
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  5. Michael G Heckman
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Correspondence to Maegan E. Roberts.

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Roberts, M.E., Riegert-Johnson, D.L., Thomas, B.C. et al. Screening for Muir-Torre Syndrome Using Mismatch Repair Protein Immunohistochemistry of Sebaceous Neoplasms. J Genet Counsel 22, 393–405 (2013). https://doi.org/10.1007/s10897-012-9552-4

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  • DOI: https://doi.org/10.1007/s10897-012-9552-4

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