title: Defective DNA mismatch repair activity is common in sebaceous neoplasms, and may be an ineffective approach to screen for Lynch syndrome.
abstract: A subset of individuals with Lynch syndrome (LS) has a variant called Muir-Torre syndrome (MTS) where patients develop multiple sebaceous neoplasms. Absence of gene expression and microsatellite instability (MSI) have been welldocumented in LS neoplasms. It is unclear whether the presence of these abnormalities in isolated sebaceous neoplasms would indicate the likely presence of otherwise unsuspected LS or MTS. 164 specimens of sporadic cutaneous sebaceous neoplasms were obtained. IHC was performed for expression of the DNA mismatch repair (MMR) genes MSH2 and MLH1. A 5-marker mononucleotide repeat microsatellite panel was analyzed to detect MSI, and two or more mutated markers were required for MSI. 164 sebaceous neoplasms were obtained from 162 patients. IHC data was successfully obtained from 162 samples and MSI data was obtained from 138 samples. 50/162 (31%) had abnormal IHC with loss of staining for either MSH2 (37/162, 23%), MLH1 (9/162, 5%) or both (4/162, 2%). 37% (52/138) of the tumors had MSI. 82% (111/136) of those with both IHC and MSI results correlated as expected. 18% (25/136) showed discordance between IHC and MSI. 69/163 (42%) had either abnormal IHC or MSI, indicating deficient DNA MMR activity. Given the substantial proportion of DNA MMR deficiency in these sebaceous neoplasms, screening for DNA MMR defects in sebaceous neoplasms would not appear to be an effective way to distinguish patients with LS or MTS from those with sporadic skin lesions and an ordinary risk of cancer.
authors: Gastrointestinal Cancer Research Laboratory, Divisions of Gastroenterology and Dermatology, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, Dallas, TX, USA, anu.lamba@baylorhealth.edu.
authors: Anu R
authors: AR
authors: Lamba
authors: Angela Y
authors: AY
authors: Moore
authors: Todd
authors: T
authors: Moore
authors: Jennifer
authors: J
authors: Rhees
authors: Mildred A
authors: MA
authors: Arnold
authors: C Richard
authors: CR
authors: Boland
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics; D053843:DNA Mismatch Repair; D006801:Humans; D053842:Microsatellite Instability; D008875:Middle Aged; D055653:Muir-Torre Syndrome / Q000235:genetics*; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein
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