Muir–Torre syndrome or phenocopy? The value of the immunohistochemical expression of mismatch repair proteins in sebaceous tumors of immunocompromised patients
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 immunoc...
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Veröffentlicht in: | Familial cancer 2014-12, Vol.13 (4), p.553-561 |
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Sprache: | eng |
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Zusammenfassung: | 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 h
MLH1
, h
MSH2
and h
MSH6
. 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. |
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ISSN: | 1389-9600 1573-7292 |
DOI: | 10.1007/s10689-014-9733-4 |