Immunoglobulin expressions are only associated with MCPyV-positive Merkel cell carcinomas but not with MCPyV-negative ones: comparison of prognosis.
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.
*Division of Molecular Pathology, Faculty of Medicine ‡Department of Pathobiological Science and Technology, School of Health Science, Faculty of Medicine, Tottori University, Yonago †Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan §Department of Histopathology, The Christie NHS Foundation Trust, Manchester, UK.
Ichiro
I
Murakami
Katsuyoshi
K
Takata
Michiko
M
Matsushita
Daisuke
D
Nonaka
Takeshi
T
Iwasaki
Satoshi
S
Kuwamoto
Masako
M
Kato
Takashi
T
Mohri
Keiko
K
Nagata
Yukisato
Y
Kitamura
Tadashi
T
Yoshino
Kazuhiko
K
Hayashi
D000368:Aged; D000369:Aged, 80 and over; D015266:Carcinoma, Merkel Cell / Q000276:immunology* / Q000401:mortality / Q000821:virology; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008297:Male; D059965:Merkel cell polyomavirus; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D027601:Polyomavirus Infections / Q000276:immunology*; D011379:Prognosis; D012878:Skin Neoplasms / Q000276:immunology* / Q000401:mortality / Q000821:virology; D014412:Tumor Virus Infections / Q000276:immunology*
D007136:Immunoglobulins