Cytokeratin 20-negative Merkel cell carcinoma is infrequently associated with the Merkel cell polyomavirus

Abstract

Merkel cell carcinoma is a rare, highly aggressive cutaneous neuroendocrine carcinoma most commonly seen in sun-damaged skin. Histologically, the tumor consists of primitive round cells with fine chromatin and numerous mitoses. Immunohistochemical stains demonstrate expression of neuroendocrine markers. In addition, cytokeratin 20 (CK20) is expressed in B95% of cases. In 2008, Merkel cell carcinoma was shown to be associated with a virus now known as Merkel cell polyomavirus in B80% of cases. Prognostic and mechanistic differences between Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative Merkel cell carcinoma may exist. There has been the suggestion that CK20-negative Merkel cell carcinomas less frequently harbor Merkel cell polyomavirus, but a systematic investigation for Merkel cell polyomavirus incidence in CK20-negative Merkel cell carcinoma has not been done. To test the hypothesis that Merkel cell polyomavirus is less frequently associated with CK20-negative Merkel cell carcinoma, we investigated 13 CK20-negative Merkel cell carcinomas from the files of the Cleveland Clinic and the University of Michigan for the virus. The presence or absence of Merkel cell polyomavirus was determined by quantitative PCR performed for Large T and small T antigens, with sequencing of PCR products to confirm the presence of Merkel cell polyomavirus. Ten of these (77%) were negative for Merkel cell polyomavirus and three (23%) were positive for Merkel cell polyomavirus. Merkel cell polyomavirus is less common in CK20-negative Merkel cell carcinoma. Larger series and clinical follow-up may help to determine whether CK20-negative Merkel cell carcinoma is mechanistically and prognostically unique.

Merkel cell carcinoma: literature review

“…It is a small novel polyomavirus with a genome consisting of double-stranded DNA. Thus, MCV may be a contributing factor in the pathogenesis of MCC [6,15,16]. The MCPyV large T antigen contains MCC tumor-specific mutations that withdraw its replication capability, however perpetuate its oncogenic functions, and the small t antigen encourages an environment propitious for carcinogenesis [17,18].…”

Comment on ‘Cytokeratin 20-negative Merkel cell carcinoma is infrequently associated with the Merkel cell polyomavirus‘

“…Although qPCR is accepted as the gold standard for MCPyV detection in MCC, there is debate about whether low levels of MCPyV represent tumorigenic virus or contamination by background wild-type virus. [1][2][3] In addition, the sensitivity of any given primer pair may vary dramatically from case to case. 1 Hence, currently there is no universally accepted threshold for considering a tumor MCPyV positive by qPCR.…”

“…[1][2][3] In addition, the sensitivity of any given primer pair may vary dramatically from case to case. 1 Hence, currently there is no universally accepted threshold for considering a tumor MCPyV positive by qPCR. We agree with Iwasaki et al that immunohistochemistry for MCPyV large T antigen (LTAg), while less…”

Viral Etiology of Merkel Cell Carcinoma:Implications in Diagnosis, Prognosis, Therapy and Prevention

“…Importantly, cytokeratin 20 (CK20) is expressed in approximately 95% of MCC cases, MCPyV in about 80% of cases, and MCPyV is less common in CK20-negative MCC [6]. The disease progression could be evaluated by means of high numbers of mitoses, proliferation and survival of tumour cells as marked by Ki-67-and Bcl-2-staining, and infiltration of lymphatic vessels [12].…”

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Merkel cell carcinoma (MCC) is a rare and a highly aggressive skin cancer of neuroendocrine origin that is frequently associated with a poor prognosis, a clonal integration of a polyomavirus (MCPyV), and a high propensy for recurrence and metastasis; its incidence increases with age, immunodeficiency and sun exposure [2,4,5,6,8]. Importantly, cytokeratin 20 (CK20) is expressed in approximately 95% of MCC cases, MCPyV in about 80% of cases, and MCPyV is less common in CK20-negative MCC [6].

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