Abstract
BackgroundApproximately 80% of Merkel cell carcinomas (MCCs) harbor Merkel cell polyomavirus (MCPyV) which monoclonally integrates into the genome and has prognostic significance. The presence or absence of MCPyV is usually diagnosed using CM2B4 immunohistochemistry (IHC) for MCPyV-large T antigen (LT) protein. However, this method poses a risk of misdiagnosis.MethodsIn this study, we determined MCPyV infection in MCCs using real-time PCR for MCPyV-LT DNA and prepared 16 cases of MCPyV-DNA-positive and -negative groups. Diagnostic sensitivity and specificity of conventional PCR for MCPyV-small T antigen (MCPyV-ST), IHC using a newly developed polyclonal antibody (ST-1) for MCPyV-ST protein (MCPyV-ST) (aa: 164–177), and in situ hybridization (ISH) as well as real-time PCR for MCPyV-ST mRNA were compared against CM2B4-IHC for sensitivity (0.94, 15/16) and specificity (0.94, 15/16).ResultsThe followings are the respective sensitivity and specificity results from examinations for MCPyV-ST gene: conventional PCR for the MCPyV-ST (0.94, 1.0), ST-1-IHC (0.69, 1.0), real-time PCR for ST mRNA (1.0, no data), ST mRNA ISH (0.94, 1.0). Each of the MCPyV-pseudonegative (1/16) and -pseudopositive (1/16) diagnoses evaluated using CM2B4-IHC were accurately corrected by examinations for MCPyV-ST or its expression as well as real-time PCR for MCPyV-LT. Sensitivity of CM2B4-IHC (0.94) was superior to that of ST-1-IHC (0.69) but equal to that of ST mRNA-ISH (0.94). Specificities of ST-1-IHC (1.0) and ST mRNA-ISH (1.0) were superior to that of CM2B4-IHC (0.94).ConclusionsTherefore, combined application of ST mRNA-ISH and ST-IHC as well as CM2B4-IHC is recommended and will contribute to the diagnostic accuracy for MCPyV infection in MCCs.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9966295741144834
Highlights
80% of Merkel cell carcinomas (MCCs) harbor Merkel cell polyomavirus (MCPyV) which monoclonally integrates into the genome and has prognostic significance
MCC cases were divided into MCPyV DNA-positive and -negative groups based on the real-time PCR data of MCPyV-large T antigen (LT)
In 16 MCPyV DNA-positive MCCs, MCPyV-LT viral copy numbers ranged from 0.06 to178.81 copies/cell
Summary
80% of Merkel cell carcinomas (MCCs) harbor Merkel cell polyomavirus (MCPyV) which monoclonally integrates into the genome and has prognostic significance. The presence or absence of MCPyV is usually diagnosed using CM2B4 immunohistochemistry (IHC) for MCPyV-large T antigen (LT) protein. This method poses a risk of misdiagnosis. Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer and Merkel cell polyomavirus (MCPyV) is monoclonally integrated into the genome of approximately 80% of MCCs [1]. IHC with CM2B4 antibody displays high sensitivity and good specificity for MCPyV detection and is usually sufficient for practical diagnosis, but it is not ideal for determining the presence or absence of MCPyV, based on reported MCC cases with pseudonegative and pseudopositive staining [3,12,13,14]. The ST gene harbors fewer mutations than the LT gene in MCPyV from MCCs [15], and the MCPyV-ST protein (MCPyVST) was detected in human MCC tumors more commonly than was MCPyV LT [16]
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