Merkel Cell Polyomavirus Detection in Extrapulmonary Small Cell Carcinoma.
Joel A Lefferts, Kathryn C Hourdequin, William A Hitzelberger, Laura J Tafe, J Marc Pipas, Marc S Ernstoff, Gregory J Tsongalis. Dartmouth-Hitchcock Medical Center and Dartmouth Medical School, Lebanon, NH
Background: A recently discovered polyomavirus associated with Merkel Cell carcinoma (MCC) has been termed Merkel Cell Polyomavirus (MCPyV). MCPyV is integrated in the tumor genome of Merkel Cell cancers and can be detected in 80% of MCC cases. Subsequent studies found that the virus could be detected in a smaller percentage of squamous cell and basal cell carcinomas but the virus was infrequently detected in other small cell or neuroendocrine lung carcinoma, which shares histological features with MCC. We investigated the presence of MCPyV in cases of extrapulmonary small cell carcinoma (ESCC), which also shares histological features with MCC.
Design: A search of hospital medical records yielded twenty-five cases of ESCC diagnosed between 2004 and 2009. Archived tissue was available sixteen of these cases were available for testing. Additionally eleven tissue specimens from four cases of Merkel cell carcinoma were used as positive controls. DNA samples extracted from sections of archived tissues specimens were each subjected to five separate real-time SYBR Green PCR assays for the detection of a human beta-globin gene and four MCPyV genomic targets to help ensure MCPyV detection despite possible variations in the viral genome.
Results: MCPyV DNA was detected in 3/16 (18.75%) of the ESCC samples and in all 11 MCC samples (four patients). In the three MCPyV-positive ESCC cases viral target was only detected by either one or two of the PCR assays while 8/11 MCPyV-positive MCC DNA samples tested positive by either three or all four assays and the remaining three MCC samples were positive by either one or two assays. The beta-globin endogenous control was detected in all samples tested.
Conclusions: Although MCC and ESCC share many histological features, MCPyV is detected with much more frequency in MCC. The possibility of a role for MCPyV in the etiology of ESCC remains uncertain. Since only one or two of the four assays detected MCPyV DNA in a limited number of ESCC cases, additional testing including DNA sequencing will be required to help confirm these results. The failure of the other assays to detect MCPyV could be due to sequence variability in the MCPyV genome. Alternatively, inadequate analytical specificity by some of the PCR assays could have resulted in false-positive results due to the presence of viral DNA with sequence similarities to MCPyV.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 233, Wednesday Morning