Research Article: Expression of Merkelcell polyomavirus (MCPyV) large T-antigen in Merkel cell carcinoma lymph node metastases predicts poor outcome

Date Published: August 1, 2017

Publisher: Public Library of Science

Author(s): Georg Haymerle, Stefan Janik, Alexandra Fochtmann, Johannes Pammer, Helga Schachner, Lucas Nemec, Michael Mildner, Roland Houben, Matthaeus Ch. Grasl, Boban M. Erovic, Pei-Yi Chu.

http://doi.org/10.1371/journal.pone.0180426

Abstract

The aim of this study was to determine the prevalence of MCPyV in Merkel cell carcinoma (MCC) primaries versus lymph node metastasis and to evaluate possible prognostic factors.

Samples of MCC primaries and lymph node metastases were stained immunohistochemically for the MCPyV large T-antigen and expression was compared to patients´ clinical outcome.

41 MCC patients were included. 33 (61%) out of 54 specimens were MCPyV-positive in the immunohistochemistry. 15 (47%) out of 32 primary tumors were positive compared to 18 (82%) out of 22 lymph node metastases. Eleven patients with positive polyomavirus expression died from the carcinoma compared to 4 patients without virus expression. Cox regression analysis showed worse disease-free survival in patients with MCPyV compared to virus-negative lymph nodes (p = 0.002).

To our knowledge this is the first study to describe a negative prognostic effect of the MCPyV expression in lymph node metastasis in MCC patients.

Partial Text

Merkel cell carcinoma (MCC) is the most aggressive skin cancer and found as neuroendocrine neoplasm predominantly in elderly white patients [1]. The incidence of 1500 new cases annually in the United States is very low compared to other cutaneous malignancies reported as and depicts a challenging disease regarding diagnosis and appropriate treatment [2,3]. MCC is typically presented as a flat or raised, isolated, red-purplish lesion with a shiny surface [4].

Since the first description of the human polyomvirus MCPyV and the development of MCC by Feng and colleagues in 2008 a series of studies have tried to identify the mechanism of DNA integration and tumor activation [4]. To date the current literature hypotheses that the viral infection occurs during early infancy via respiratory, cutaneous or fecal-oral routes [9,10]. Virus activation is triggered by aging, UV radiation, immunodeficiency due to HIV infection or immunosuppressive therapy. Thus, there might be two possible pathogenetic pathways of MCC in the human. Firstly, a virus induced oncogenesis in patients with a high viral load of the tumor and secondly, a MCC variant which is not viral associated but rather induced by UV radiation in sun-exposed areas of the skin [11,12]. The prognostic significance of MCPyV LTA in MCC primaries or lymph node metastates remains unclear. We therefore, conducted a retrospective analysis of MCC patients and correlated MCPyV LTA in lymph node metastes with clinical outcome.

 

Source:

http://doi.org/10.1371/journal.pone.0180426

 

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