title: Identification of CXCL13 as a new marker for follicular dendritic cell sarcoma.
abstract: 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 (T(H)F) as additional CXCL13 producers in the germinal centre and the neoplastic counterpart of T(H)F (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.
authors.affiliation: Department of Pathology, Spedali Civili di Brescia, University of Brescia, Brescia, Italy. william.vermi@gmail.com
authors.forename: W
authors.initials: W
authors.lastname: Vermi
authors.forename: S
authors.initials: S
authors.lastname: Lonardi
authors.forename: D
authors.initials: D
authors.lastname: Bosisio
authors.forename: M
authors.initials: M
authors.lastname: Uguccioni
authors.forename: G
authors.initials: G
authors.lastname: Danelon
authors.forename: S
authors.initials: S
authors.lastname: Pileri
authors.forename: C
authors.initials: C
authors.lastname: Fletcher
authors.forename: S
authors.initials: S
authors.lastname: Sozzani
authors.forename: F
authors.initials: F
authors.lastname: Zorzi
authors.forename: G
authors.initials: G
authors.lastname: Arrigoni
authors.forename: C
authors.initials: C
authors.lastname: Doglioni
authors.forename: M
authors.initials: M
authors.lastname: Ponzoni
authors.forename: F
authors.initials: F
authors.lastname: Facchetti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D005871:Castleman Disease / Q000276:immunology; D054382:Chemokine CXCL13 / Q000032:analysis* / Q000235:genetics; D020566:Dendritic Cells, Follicular / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D014066:Palatine Tonsil / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D054380:Receptors, CXCR5 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012509:Sarcoma / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D012333:RNA, Messenger; D054380:Receptors, CXCR5