Startseite Role of microsatellite instability, immunohistochemistry and mismatch repair germline aberrations in immunosuppressed transplant patients: a phenocopy dilemma in Muir-Torre syndrome
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Role of microsatellite instability, immunohistochemistry and mismatch repair germline aberrations in immunosuppressed transplant patients: a phenocopy dilemma in Muir-Torre syndrome

  • Giovanni Ponti EMAIL logo , Marco Manfredini , Giovanni Pellacani und Aldo Tomasi
Veröffentlicht/Copyright: 25. März 2016
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 54 Heft 11

Abstract

Sebaceous tumours and keratoacanthomas are uncommon neoplasms that constitute important clinical criteria for Muir-Torre syndrome (MTS) diagnosis. In MTS patients, the increased risk of developing synchronous or metachronous visceral malignancies is characterised by autosomal dominant inheritance. However, there are further conditions, other than MTS, that increase the risk of sebaceous neoplasms, e.g. iatrogenic immunosuppression. In this latter scenario, the sebaceous tumours can present microsatellite instability (MSI) and loss of mismatch repair (MMR) proteins, characteristic of hereditary syndromes, even in the absence of MMR germline mutations. In this article, we examine transplant probands in which the immunosuppressive therapies unmask the MTS cutaneous phenotypes, showing MSI and loss of MMR protein expression, as demonstrated by immunohistochemistry (IHC). Furthermore, MMR genes sequencing analysis identified the presence of germline mutations in MTS-suspected individuals, in the absence of a visceral MTS phenotype. It is well known that immunosuppression plays a central role in the development of sebaceous tumours in both MTS and in non-syndromic settings. Sebaceous skin tumours’ MSI status and IHC profiles can be influenced by epigenetic or iatrogenic factors; however, they constitute valuable tools and a cost-effective approach to screen individuals who otherways should undergo MMR genes direct sequencing in the context of immunosuppression. In this complex setting, the choice of the immunosuppressive drug becomes a critical decision for the management of both MTS and sporadic transplant patients, which may benefit from the administration of immunosuppressive drugs, resulting in a low impact on skin cancerogenesis.

Keywords: immunohistochemistry; immunosuppressed transplant patients; microsatellite instability; mismatch repair germline aberrations; Muir-Torre syndrome phenocopy
Corresponding author: Dr. Giovanni Ponti, Department of Surgical, Medical, Dental and Morphological Sciences with Interest Transplant, Oncological and Regenerative Medicine, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy, Phone: +39594224748, Fax: +39594224271, E-mail:

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted article and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organisation(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2015-12-8
Accepted: 2016-2-3
Published Online: 2016-3-25
Published in Print: 2016-11-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Editorials
  3. CCLM Award for the Most Cited Paper Recently Published
  4. Laboratory economics. Risk or opportunity?
  5. Reviews
  6. Molecular diagnosis and precision medicine in allergy management
  7. The insulin autoimmune syndrome (IAS) as a cause of hypoglycaemia: an update on the pathophysiology, biochemical investigations and diagnosis
  8. Opinion Paper
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  10. Genetics and Molecular Diagnostics
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  40. Keeping Ebola out of the lab: a practical solution on how to analyze Ebola associated blood anomalies
  41. Standardized fixation process is crucial to permit molecular analyses in formalin-fixed and paraffin-embedded melanoma samples
  42. Congress Abstracts
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https://doi.org/10.1515/cclm-2015-1210
Schlagwörter für diesen Artikel
immunohistochemistry; immunosuppressed transplant patients; microsatellite instability; mismatch repair germline aberrations; Muir-Torre syndrome phenocopy

Artikel in diesem Heft

  1. Frontmatter
  2. Editorials
  3. CCLM Award for the Most Cited Paper Recently Published
  4. Laboratory economics. Risk or opportunity?
  5. Reviews
  6. Molecular diagnosis and precision medicine in allergy management
  7. The insulin autoimmune syndrome (IAS) as a cause of hypoglycaemia: an update on the pathophysiology, biochemical investigations and diagnosis
  8. Opinion Paper
  9. Role of microsatellite instability, immunohistochemistry and mismatch repair germline aberrations in immunosuppressed transplant patients: a phenocopy dilemma in Muir-Torre syndrome
  10. Genetics and Molecular Diagnostics
  11. Time and tumor type (primary or metastatic) do not influence the detection of BRAF/NRAS mutations in formalin fixed paraffin embedded samples from melanomas
  12. False low holotranscobalamin levels in a patient with a novel TCN2 mutation
  13. General Clinical Chemistry and Laboratory Medicine
  14. Quality performance of laboratory testing in pharmacies: a collaborative evaluation
  15. Cost evaluation of clinical laboratory in Taiwan’s National Health System by using activity-based costing
  16. Impact of sample processing on the measurement of circulating microparticles: storage and centrifugation parameters
  17. HbA1c: EQA in Germany, Belgium and the Netherlands using fresh whole blood samples with target values assigned with the IFCC reference system
  18. Iohexol clearance in unstable critically ill patients: a tool to assess glomerular filtration rate
  19. Characteristics of Chinese patients with antiphospholipid syndrome and the ability of lupus anticoagulant assays to identify them
  20. Reference Values and Biological Variations
  21. Distribution of soluble suppression of tumorigenicity 2 (sST2), N-terminal pro-brain natriuretic peptide (NT-proBNP), high sensitive troponin I and high-sensitive troponin T in umbilical cord blood
  22. Hematology and Coagulation
  23. Evaluation of Mindray BC-6800 body fluid mode for automated cerebrospinal fluid cell counting
  24. Cancer Diagnostics
  25. Increased sialylation and reduced fucosylation of exfoliated cervical cells are potential markers of carcinogenesis in the cervix
  26. Cardiovascular Diseases
  27. High incidence of macrotroponin I with a high-sensitivity troponin I assay
  28. Infectious Diseases
  29. Prospective evaluation of biomarkers for prediction of quality of life in community-acquired pneumonia
  30. Letter to the Editor
  31. The use of extra-analytical phase quality indicators by clinical laboratories: the results of an international survey
  32. Quality of reporting of diagnostic test accuracy studies in medical laboratory journals
  33. Impact of under-filled blood collection tubes containing K2EDTA and K3EDTA as anticoagulants on automated complete blood count (CBC) testing
  34. Stability of plasma albumin depends on measurement method
  35. Evaluation of screening method for Bence Jones protein analysis
  36. Reference intervals for the Kryptor second-generation chromogranin A assay
  37. Evaluation of an automated urinary iodine measurement using AU5800 analyzer with AutoLab Iodine reagent
  38. Evaluation of the accuracy of complete blood count for insufficient blood samples
  39. The use of a “gray zone” considering measurement uncertainty in pharmacological tests. The serum growth hormone stimulation test as an example
  40. Keeping Ebola out of the lab: a practical solution on how to analyze Ebola associated blood anomalies
  41. Standardized fixation process is crucial to permit molecular analyses in formalin-fixed and paraffin-embedded melanoma samples
  42. Congress Abstracts
  43. 48th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC – Laboratory Medicine)
  44. 8th Santorini Conference Systems Medicine and Personalised Health and Therapy
  45. Congress of Laboratory Medicine and Clinical Chemistry
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