title: Enhanced detection of microsatellite instability and mismatch repair gene expression in cutaneous squamous cell carcinomas.
abstract: BACKGROUND
  Microsatellite instability (MSI) is a phenotypic characteristic of tumors with biallelic inactivation of mismatch repair genes, such as MSH2 or MLH1, and contributes to malignant transformation.
  
  
  OBJECTIVE
  The aim of this study was to examine the prevalence of MSI in cutaneous squamous cell carcinoma (SCC) using a PCR and fluorescent-based detection system. These methods of analysis offer several advantages over the use of silver staining and autoradiographic techniques. We also aimed to determine if MSI status correlated with expression of the MSH2 and MLH1 mismatch repair proteins in these cutaneous SCC samples.
  
  
  METHODS
  The MSI status of 22 histologically confirmed invasive cutaneous SCC samples were analyzed at five microsatellite markers (the National Cancer Institute's Bethesda panel of two mononucleotide and three dinucleotide markers) using a PCR and fluorescent-based detection system. Immunohistochemical analysis of MSH2 and MLH1 protein expression was also carried out on the SCC samples.
  
  
  RESULTS
  Only one case of cutaneous SCC displayed MSI. This was found at just one of five markers, and thus was low frequency MSI. All 22 cutaneous SCC cases strongly expressed MSH2 protein. Eighteen (82%) of the cutaneous SCC cases showed moderate to strong expression of MLH1 protein. The remaining four cases of cutaneous SCC were negative for MLH1 protein. Therefore, the majority of the SCC patients analyzed showed a correlation between absence of MSI and expression of MSH2 and MLH1 proteins.
  
  
  CONCLUSIONS
  MSI is uncommon in cutaneous SCC. In addition, MSH2 was strongly expressed in all SCC samples analyzed and appeared to be upregulated when compared with the corresponding normal tissue. MLH1 protein was not detected in 4 of 22 SCC cases, although it was expressed in the corresponding normal tissue, suggesting that inactivation of MLH1 may be a late event in a subset of invasive SCC cases.
authors.affiliation: Molecular Oncology Laboratory, Pathology Department, Royal College of Surgeons in Ireland (RCSI) and the Beaumont Hospital, Dublin, Ireland.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Gray
authors.forename: Elaine W
authors.initials: EW
authors.lastname: Kay
authors.forename: Mary
authors.initials: M
authors.lastname: Leader
authors.forename: Mohamed J E M F
authors.initials: MJ
authors.lastname: Mabruk
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D053843:DNA Mismatch Repair; D015870:Gene Expression; D006801:Humans; D053842:Microsatellite Instability; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein