Reviewing the current evidence supporting early B-cells as the cellular origin of Merkel cell carcinoma. (August 2017)

• Record Type: Journal Article
• Authors: Sauer, C.M.; Haugg, A.M.; Chteinberg, E.; Rennspiess, D.; Winnepenninckx, V.; Speel, E.-J.; Becker, J.C.; Kurz, A.K.; zur Hausen, A.
• Is Part Of: Critical reviews in oncology/hematology. Volume 116(2017)
• Page Start: 99
• Page End: 105
• Publication Date: 2017-08
• Subjects: MC Merkel cell -- MCC Merkel cell carcinoma -- MCPyV Merkel cell polyoma virus -- TdT terminal deoxynucleotidyl transferase -- IHC immunohistochemistry -- Ig immunoglobulin -- CK cytokeratin -- CD cluster of differentiation -- HSC pluripotent hematopoietic stem cell -- EBF-1 early B-cell factor 1 -- PAX-5 paired-box gene 5 -- NSE neuron-specific enolase; Merkel cell carcinoma -- Merkel cell polyoma virus -- Cell of origin -- B-cell differentiation -- Lymphoma -- Merkel cell -- Stem cell -- Oncogenesis -- Pathogenesis -- Cutaneous B-cell lymphoma; Oncology -- Periodicals; Hematology -- Periodicals; 616.994
• DOI: 10.1016/j.critrevonc.2017.05.009
• Languages: English
• ISSNs: 1040-8428

Abstract

Abstract: Merkel cell carcinoma (MCC) is a highly malignant skin cancer characterized by early metastases and poor survival. Although MCC is a rare malignancy, its incidence is rapidly increasing in the U.S. and Europe. The discovery of the Merkel cell polyomavirus (MCPyV) has enormously impacted our understanding of its etiopathogenesis and biology. MCCs are characterized by trilinear differentiation, comprising the expression of neuroendocrine, epithelial and B-lymphoid lineage markers. To date, it is generally accepted that the initial assumption of MCC originating from Merkel cells (MCs) is unlikely. This is owed to their post-mitotic character, absence of MCPyV in MCs and discrepant protein expression pattern in comparison to MCC. Evidence from mouse models suggests that epidermal/dermal stem cells might be of cellular origin in MCC. The recently formulated hypothesis of MCC originating from early B-cells is based on morphology, the consistent expression of early B-cell lineage markers and the finding of clonal immunoglobulin chain rearrangement in MCC cells. In this review we elaborate on the cellular ancestry of MCC, the identification of which could pave the way for novel and more effective therapeutic regimens.