Immunoglobulin Expressions Are Only Associated With MCPyV-positive Merkel Cell Carcinomas But Not With MCPyV-negative Ones

Abstract

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer, often associated with Merkel cell polyomavirus (MCPyV). Recently, immunoglobulin (Ig) expression was reported in MCC, thereby suggesting that B cells might be their cellular ancestors. We tested 30 MCCs (20 MCPyV-positive and 10 MCPyV-negative) using immunohistochemistry for the expressions of IgG, IgA, IgM, Igκ, Igλ, terminal desoxynucleotidyl transferase, paired box gene 5 (PAX5), octamer transcription factor-2 (Oct-2), and sex-determining region Y-box 11 (SOX11). We performed in situ hybridization for Igκ-mRNA or Igλ-mRNA and Ig heavy chain (IgH) gene rearrangement (IgH-R) analyses. The expressions of PAX5, TdT, Oct-2, and SOX11 were not significantly different between MCPyV-positive and MCPyV-negative MCCs. At least 1 of IgG, IgA, IgM, or Igκ was expressed in MCPyV-positive (14/20, 70%) and none in MCPyV-negative MCCs (P=0.0003). There was a higher tendency for Igκ-mRNA expression (7/19, using in situ hybridization) and IgH-R (10/20, using polymerase chain reaction) in MCPyV-positive than in MCPyV-negative MCCs (0/10 and 2/10, respectively), thus suggesting a different Ig production pattern and pathogenesis between the 2 types of MCC. Ig expression or IgH-R in MCPyV-positive MCCs might be associated with MCPyV gene integration or expression in cancer cells but do not necessarily suggest a B-cell origin for MCCs. IgH expression or IgH-R nonsignificantly correlated with improved prognosis. However, these might be important factors that influence the survival of neoplastic cells and might allow the development of novel therapies for patients with MCPyV-positive MCCs.

Absence of immunoglobulin heavy chain rearrangement in primary Merkel cell carcinomas

“…found that at least one immunoglobulin (IgG, IgA, IgM or Igκ) was expressed in MCPyV‐positive MCCs (14/20, 70%) and none in MCPyV‐negative MCCs. They found a higher tendency for Igκ mRNA expression (7/19) and IgH rearrangement (10/20, using PCR) in MCPyV‐positive than in MCPyV‐negative MCCs (0/10 and 2/10, respectively), thus suggesting a different immunoglobulin production pattern and pathogenesis between the two subtypes of MCC . Our results indicating that B‐cell clonality is usually absent in MCC support the observations by Zur Hausen et al ., who detected IgH and/or IgK rearrangement in only 3 of the 18 cases they analysed.…”

“…Evidence from animal models suggests that epidermal/dermal stem cells might be the cellular origin of MCC. The recently formulated hypothesis of MCC originating from pro/pre‐B or pre‐B cells is supported by cell morphology, the consistent expression of early B‐cell lineage markers and the finding of clonal immunoglobulin chain rearrangement in MCC cells . Murakami et al .…”

“…The recently formulated hypothesis of MCC originating from pro/pre‐B or pre‐B cells is supported by cell morphology, the consistent expression of early B‐cell lineage markers and the finding of clonal immunoglobulin chain rearrangement in MCC cells . Murakami et al . found that at least one immunoglobulin (IgG, IgA, IgM or Igκ) was expressed in MCPyV‐positive MCCs (14/20, 70%) and none in MCPyV‐negative MCCs.…”

The expression of terminal deoxynucleotidyl transferase and paired box gene 5 in Merkel cell carcinomas and its relation to the presence of Merkel cell polyomavirus DNA

“…Expression of B‐lymphoid lineage markers in MCC is frequent (Table ), including TdT and PAX5. These markers are recurrent in MCC in both primary cutaneous tumors and metastatic lymph nodes . Nearly, 90% of the tumors reported express PAX5 and 65% express TdT .…”

Merkelzellkarzinom: kutane Manifestation einer hochmalignen Prä-/pro-B-Zell-Neoplasie?

“…1). Darüber hi- positiven MZK nachgewiesen [35]. In unserer Testreihe von 21 MZK konnten wir bei fast allen MZK eine Expression der einen oder anderen Ig-Klasse oder Ig-Bestandteile feststellen.…”