Primary and secondary immunodepressive conditions are associated with an increased incidence of sebaceous tumors. Microsatellite instability (MSI) and lack of expression of mismatch repair (MMR) proteins, typical markers of Muir-Torre/Lynch heredo-familial settings, can be recognized also in immunocompromised patients. We aimed to carry on a systematic examination of clinical, immunohistochemical, biomolecular features of sebaceous tumors arising in immunocompromised and immunocompetent patients between 1986 and 2012. Microsatellite screening, immunohistochemical analysis and genetic testing were performed for hMLH1, hMSH2 and hMSH6. Methylation status of MMR genes was checked in cases with immunohistochemistry (IHC) loss of MMR proteins expression and no germline mutations. Fifteen patients had a personal history of visceral carcinomas fulfilling diagnostic criteria for Muir-Torre syndrome. In this cohort, IHC analysis, MSI status and genetic testing were in agreement, showing eight MSH2 and two MLH1 germline mutations. Five patients were immunosuppressed and their sebaceous tumors showed a lack of MSH2/MSH6 expression, although just one case with positive family history for visceral cancer harbored a germline mutation. In immunosuppressed patients, loss of IHC for MMR proteins is not necessarily secondary to MMR germline mutations. IHC false positives are probably due to epigenetic alterations. MSI and lack of expression of MMR proteins can be recognized also in immunocompromised patients without MMR germline mutations.

Muir-Torre syndrome or phenocopy? The value of the immunohistochemical expression of mismatch repair proteins in sebaceous tumors of immunocompromised patients / Ponti, Giovanni; Pellacani, Giovanni; Ruini, Cristel; Percesepe, Antonio; Longo, Caterina; Mandel, Victor Desmond; Crucianelli, Francesca; Gorelli, Greta; Tomasi, Aldo. - In: FAMILIAL CANCER. - ISSN 1389-9600. - STAMPA. - 13:4(2014), pp. 553-561. [10.1007/s10689-014-9733-4]

Muir-Torre syndrome or phenocopy? The value of the immunohistochemical expression of mismatch repair proteins in sebaceous tumors of immunocompromised patients

PONTI, Giovanni;PELLACANI, Giovanni;RUINI, Cristel;PERCESEPE, Antonio;LONGO, Caterina;MANDEL, Victor Desmond;TOMASI, Aldo
2014

Abstract

Primary and secondary immunodepressive conditions are associated with an increased incidence of sebaceous tumors. Microsatellite instability (MSI) and lack of expression of mismatch repair (MMR) proteins, typical markers of Muir-Torre/Lynch heredo-familial settings, can be recognized also in immunocompromised patients. We aimed to carry on a systematic examination of clinical, immunohistochemical, biomolecular features of sebaceous tumors arising in immunocompromised and immunocompetent patients between 1986 and 2012. Microsatellite screening, immunohistochemical analysis and genetic testing were performed for hMLH1, hMSH2 and hMSH6. Methylation status of MMR genes was checked in cases with immunohistochemistry (IHC) loss of MMR proteins expression and no germline mutations. Fifteen patients had a personal history of visceral carcinomas fulfilling diagnostic criteria for Muir-Torre syndrome. In this cohort, IHC analysis, MSI status and genetic testing were in agreement, showing eight MSH2 and two MLH1 germline mutations. Five patients were immunosuppressed and their sebaceous tumors showed a lack of MSH2/MSH6 expression, although just one case with positive family history for visceral cancer harbored a germline mutation. In immunosuppressed patients, loss of IHC for MMR proteins is not necessarily secondary to MMR germline mutations. IHC false positives are probably due to epigenetic alterations. MSI and lack of expression of MMR proteins can be recognized also in immunocompromised patients without MMR germline mutations.
2014
27-giu-2014
13
4
553
561
Muir-Torre syndrome or phenocopy? The value of the immunohistochemical expression of mismatch repair proteins in sebaceous tumors of immunocompromised patients / Ponti, Giovanni; Pellacani, Giovanni; Ruini, Cristel; Percesepe, Antonio; Longo, Caterina; Mandel, Victor Desmond; Crucianelli, Francesca; Gorelli, Greta; Tomasi, Aldo. - In: FAMILIAL CANCER. - ISSN 1389-9600. - STAMPA. - 13:4(2014), pp. 553-561. [10.1007/s10689-014-9733-4]
Ponti, Giovanni; Pellacani, Giovanni; Ruini, Cristel; Percesepe, Antonio; Longo, Caterina; Mandel, Victor Desmond; Crucianelli, Francesca; Gorelli, Greta; Tomasi, Aldo
File in questo prodotto:
File Dimensione Formato  
Muir-Torre syndrome or phenocopy - The value of the immunohistochemical expression of mismatch repair proteins in sebaceous tumors of immunocompromised patients.pdf

Accesso riservato

Descrizione: Articolo principale
Tipologia: Versione pubblicata dall'editore
Dimensione 369.03 kB
Formato Adobe PDF
369.03 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1028714
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 13
  • ???jsp.display-item.citation.isi??? 13
social impact