Merkel cell carcinoma of unknown primary: Immunohistochemical and molecular analyses reveal distinct UV-signature/MCPyV-negative and high immunogenicity/MCPyV-positive profiles

Piotr Donizy, Joanna P. Wróblewska, Dora Dias-Santagata, Katarzyna Woznica, Przemyslaw Biecek, Mark C. Mochel, Cheng Lin Wu, Janusz Kopczynski, Malgorzata Pieniazek, Janusz Ryś, Andrzej Marszalek, Mai P. Hoang

研究成果: Article同行評審

1 引文 斯高帕斯(Scopus)

摘要

Background: Merkel cell carcinomas of unknown primary (MCC-UPs) are defined as deep-seated tumors without an associated cutaneous tumor. Although the distinction has important clinical implications, it remains unclear whether these tumors represent primary tumors of lymph nodes or metastatic cutaneous primaries. Methods: We compared the immunohistochemical profiles of four groups of MCCs (Merkel cell polyomavirus (MCPyV)-positive UP, MCPyV-negative UP, MCPyV-positive known primary (KP), and MCPyV-negative KP) using B-cell and pre-B-cell markers, cell cycle regulating proteins, follicular stem cell markers, and immune markers, and performed next generation and Sanger sequencing. Results: Virus-positive and virus-negative MCC-UPs exhibited an immunoprofile similar to virus-positive and virus-negative primary cutaneous MCCs, respectively. MCC-UP tumors (both virus-positive and-negative) were immunogenic with similar or even higher tumoral PD-L1 expression and intratumoral CD8 and FoxP3 infiltrates in comparison to MCPyV-positive cutaneous tumors. In addition, similar to primary cutaneous MCCs, MCPyV-negative MCC-UPs exhibited UV signatures and frequent high tumor mutational burdens, whereas few molecular alterations were noted in MCPyV-positive MCC-UPs. Conclusions: Our results showed distinct UV-signatures in MCPyV-negative tumors and high immunogenicity in MCPyV-positive tumors. Although additional studies are warranted for the MCPyV-positive cases, our findings are supportive of a cutaneous metastatic origin for MCPyV-negative MCC-UP tumors.

原文English
文章編號1621
期刊Cancers
13
發行號7
DOIs
出版狀態Published - 2021 四月 1

All Science Journal Classification (ASJC) codes

  • 腫瘤科
  • 癌症研究

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