title: Plasma cells in primary melanoma. Prognostic significance and possible role of IgA.
abstract: Melanoma is not only one of the most immunogenic cancers but also one of the most effective cancers at subverting host immunity. The role of T lymphocytes in tumor immunity has been extensively studied in melanoma, whereas less is known about the importance of B lymphocytes. The effects of plasma cells (PCs), in particular, are still obscure. The aim of this study was to characterize pathological features and clinical outcome of primary cutaneous melanomas associated with PCs. Moreover, we investigated the origins of the melanoma-associated PCs. Finally, we studied the outcome of patients with primary melanomas with PCs. We reviewed 710 melanomas to correlate the presence of PCs with histological prognostic markers. Immunohistochemistry for CD138 and heavy and light chains was performed in primary melanomas (PM) and in loco-regional lymph nodes (LN), both metastatic and not metastatic. In three PM and nine LN with frozen material, VDJ-rearrangement was analyzed by Gene Scan Analysis. Survival analysis was performed on a group of 85 primary melanomas >2 mm in thickness. Forty-one cases (3.7%) showed clusters/sheets of PCs. PC-rich melanomas occurred at an older age and were thicker, more often ulcerated and more mitotically active (P<0.05). PCs were polyclonal and often expressed IgA in addition to IgG. In LN, clusters/sheets of IgA+ PCs were found both in the sinuses and subcapsular areas. Analysis of VDJ-rearrangements showed the IgA to be oligoclonal. Melanomas with clusters/sheets of PCs had a significantly worse survival compared with melanomas without PCs while, interestingly, melanomas with sparse PCs were associated with a better clinical outcome (P=0.002). In conclusion, melanomas with sheets/clusters of PCs are associated with worse prognosis. IgG and IgA are the isotypes predominantly produced by these PCs. IgA oligoclonality suggests an antigen-driven response that facilitates melanoma progression by a hitherto unknown mechanism.
authors: Laboratory of Translational Cell and Tissue Research, University of Leuven, KUL, Leuven, Belgium.|Università Degli Studi di Milano-Bicocca, Milan, Italy.
authors: Francesca M
authors: FM
authors: Bosisio
authors: Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
authors: James S
authors: JS
authors: Wilmott
authors: Laboratory of Translational Cell and Tissue Research, University of Leuven, KUL, Leuven, Belgium.
authors: Nathalie
authors: N
authors: Volders
authors: Ludwig Institute for Cancer Research and de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
authors: Marjorie
authors: M
authors: Mercier
authors: Laboratory of Translational Cell and Tissue Research, University of Leuven, KUL, Leuven, Belgium.
authors: Jasper
authors: http://orcid.org/0000-0002-7129-2990
authors: J
authors: Wouters
authors: Department of Surgical Oncology, UZ Gasthuisberg and KU Leuven, Leuven, Belgium.
authors: Marguerite
authors: M
authors: Stas
authors: Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Willeke Am
authors: WA
authors: Blokx
authors: Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
authors: Daniela
authors: D
authors: Massi
authors: Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
authors: John F
authors: JF
authors: Thompson
authors: Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.|Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
authors: Richard A
authors: RA
authors: Scolyer
authors: Ludwig Institute for Cancer Research and de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
authors: Nicolas
authors: N
authors: van Baren
authors: Laboratory of Translational Cell and Tissue Research, University of Leuven, KUL, Leuven, Belgium.
authors: Joost J
authors: JJ
authors: van den Oord
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D006801:Humans; D007070:Immunoglobulin A; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology*; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D055815:Young Adult
chemical_list: D007070:Immunoglobulin A