No conflicts of interest were declared.
Identification of CXCL13 as a new marker for follicular dendritic cell sarcoma†
Article first published online: 31 JUL 2008
Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 216, Issue 3, pages 356–364, November 2008
How to Cite
Vermi, W., Lonardi, S., Bosisio, D., Uguccioni, M., Danelon, G., Pileri, S., Fletcher, C., Sozzani, S., Zorzi, F., Arrigoni, G., Doglioni, C., Ponzoni, M. and Facchetti, F. (2008), Identification of CXCL13 as a new marker for follicular dendritic cell sarcoma. J. Pathol., 216: 356–364. doi: 10.1002/path.2420
- Issue published online: 7 OCT 2008
- Article first published online: 31 JUL 2008
- Accepted manuscript online: 31 JUL 2008 12:00AM EST
- Manuscript Accepted: 22 JUL 2008
- Manuscript Revised: 21 JUL 2008
- Manuscript Received: 16 JUN 2008
- Nobel Project Fondazione Cariplo
- INNOCHEM. Grant Numbers: LSHB-CT-2005-518167, LSHG-CT-2003-502935
- Swiss National Science Foundation. Grant Number: 3100A0-118048/1, to MU
- lymphoid organs;
- follicular dendritic cell sarcoma, Castleman's disease
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 THF (CD4+ tumour 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 ten cases of FDC-S strongly and diffusely express this chemokine. This observation was confirmed at mRNA 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 (IgD+ and TCL1+). In conclusion, this study demonstrates that CXCL13 is produced by dysplastic and neoplastic FDCs and can be instrumental in recruiting intratumoural CXCR5+ lymphocytes. In addition to the potential biological relevance of this expression, the use of reagents directed against CXCL13 can be useful to properly identify the origin of spindle cell and epithelioid neoplasms. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.