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Enhanced Detection of Microsatellite Instability and Mismatch Repair Gene Expression in Cutaneous Squamous Cell Carcinomas

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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.

Aims: 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.

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Acknowledgments

The authors would like to thank the Medical staff of the Dermatology clinic at the Beaumont Hospital for providing samples from patients with skin cancer; we also thank Dr Muna Sabah and Mr David Butler for technical assistance. Also, we would like to acknowledge the Irish Cancer Society and the Royal College of Surgeons in Ireland (RCSI) for their financial support.

The authors have no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. Molecular Oncology Laboratory, Pathology Department, Royal College of Surgeons in Ireland (RCSI) and the Beaumont Hospital, Dublin, Ireland

    Sarah E. Gray, Elaine W. Kay, Mary Leader &  Mohamed J. E. M. F. Mabruk

  2. Advanced Medical and Dental Institute, University Sains Malaysia, Eureka Komplex, Penang, USM, 11800, Malaysia

    Mohamed J. E. M. F. Mabruk

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  1. Sarah E. Gray
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  2. Elaine W. Kay
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  4. Mohamed J. E. M. F. Mabruk
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Correspondence to Mohamed J. E. M. F. Mabruk.

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Gray, S.E., Kay, E.W., Leader, M. et al. Enhanced Detection of Microsatellite Instability and Mismatch Repair Gene Expression in Cutaneous Squamous Cell Carcinomas. Mol Diag Ther 10, 327–334 (2006). https://doi.org/10.1007/BF03256208

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