4.7 Article

Identification of CXCL13 as a new marker for follicular dendritic cell sarcoma

Journal

JOURNAL OF PATHOLOGY
Volume 216, Issue 3, Pages 356-364

Publisher

JOHN WILEY & SONS LTD
DOI: 10.1002/path.2420

Keywords

CXCL13; chemokines; lymphoid organs; follicular dendritic cell sarcoma; Castleman's disease

Funding

  1. Nobel Project Fondazione Cariplo
  2. European Union FP6 [LSHB-CT-2005-518167, LSHG-CT-2003-502935]
  3. Swiss National Science Foundation [3100A0-118048/1]
  4. AIRC (Associazione Italiana per la Ricerca SUI Canero)
  5. Fondazione Beretta (Brescia, Italy)

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The homeostatic chemokine CXCL13 is preferentially produced in B-follicles and is crucial in the lymphoid organ development by attracting B-lymphocytes that express its selective receptor CXCR5. Follicular dendritic cells (FDCs) have been identified as the main cellular source of this chemokine in lymphoid organs. Recently, genome-wide approaches have Suggested follicular CD4 T-helper cells (THF) as additional CXCL13 producers in the germinal centre and the neoplastic counterpart of TIIF (CD4+ turnour T-cells in angioimmunoblastic T-cell lymphoma) retains the capability of producing this chemokine. In contrast, no data are available on CXCL13 expression on FDC sarcoma (FDC-S) cells. By using multiple approaches, we investigated the expression of CXCL13 at mRNA and protein level in reactive and neoplastic FDCs. In reactive lymph nodes and tonsils, CXCL13 protein is mainly expressed by a subset of FDCs in B-cell follicles. CXCL13 is maintained during FDC transformation, since both dysplastic FDCs from 13 cases of Castleman's disease and neoplastic FDCs from tell cases of FDC-S strongly and diffusely express this chemokine. This observation was confirmed at nRNA level by using RT-PCR and in situ hybridization. Of note, no CXCL13 reactivity was observed in a cohort of epithelial and mesenchymal neoplasms potentially mimicking FDC-S. FDC-S are commonly associated with a dense intratumoural inflammatory infiltrate and immunohistochemistry showed that these lymphocytes express the CXCL13 receptor CXCR5 and are mainly of mantle zone B-cell derivation (IgI)+ and TCLI+). In conclusion, this study demonstrates that CXCL13 is produced by dysplastic and neoplastic FDCs and call be instrumental in recruiting intratumoural CXCR5+ lymphocytes. In addition to the potential biological relevance of this expression, the use of reagents directed against CXCL13 call be useful to properly identify the origin of spindle cell and epithelioid neoplasms. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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