Plasma cells in primary melanoma. Prognostic significance and possible role of IgA

被引:52
作者
Bosisio, Francesca M. [1 ,2 ]
Wilmott, James S. [3 ]
Volders, Nathalie [1 ]
Mercier, Marjorie [4 ,5 ]
Wouters, Jasper [1 ]
Stas, Marguerite [6 ,7 ]
Blokx, Willeke A. M. [8 ]
Massi, Daniela [9 ]
Thompson, John F. [3 ]
Scolyer, Richard A. [3 ,10 ]
van Baren, Nicolas [4 ,5 ]
van den Oord, Joost J. [1 ]
机构
[1] Univ Leuven, KUL, Lab Translat Cell & Tissue Res, Minderbroedersstr 12 Blok P Bus 1032, B-3000 Leuven, Belgium
[2] Univ Milano Bicocca, Milan, Italy
[3] Univ Sydney, Melanoma Inst Australia, Sydney, NSW 2006, Australia
[4] Catholic Univ Louvain, Ludwig Inst Canc Res, B-1200 Brussels, Belgium
[5] Catholic Univ Louvain, de Duve Inst, B-1200 Brussels, Belgium
[6] Univ Hosp Gasthuisberg, Dept Surg Oncol, Leuven, Belgium
[7] Katholieke Univ Leuven, Leuven, Belgium
[8] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands
[9] Univ Florence, Dept Surg & Translat Med, Florence, Italy
[10] Royal Prince Alfred Hosp, Dept Tissue Pathol & Diagnost Oncol, Camperdown, NSW 2050, Australia
基金
欧盟地平线“2020”;
关键词
TUMOR-INFILTRATING LYMPHOCYTES; IMMUNE CELLS; LYMPHOID STRUCTURES; B-CELLS; CANCER; SKIN; MICROENVIRONMENT; POLARIZATION; PLASTICITY; MPDL3280A;
D O I
10.1038/modpathol.2016.28
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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.
引用
收藏
页码:347 / 358
页数:12
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